SlideShare a Scribd company logo
1 of 21
Download to read offline
Clearance Concept



   Anas Bahnassi PhD RPh
Lecture Objectives
After the completion of this lecture the student
should be able to:
1. Define clearance and extraction ratio and describe the relationship
   between them.
2. Distinguish clearance from elimination rate and elimination rate
   constant.
3. Explain the dependence of elimination half life on apparent
   volume of distribution and clearance
4. Calculate area under the plasma drug concentration versus time
   curve by use of the trapezoidal rule and by other methods
5. Calculate a patient’s creatinine clearance using the appropriate
   equation
6. Calculate dosing adjustments of a renally excreted drug in
   patients with various degrees of renal impairment (dysfunction).
A Physiological Approach to
Understand Clearance
Concept                                        Site of
                                               Action



                                                          Heart
            Clearing Organ
                                                         (Pump)
            (Kidney/Liver)




                              The blood exiting the eliminating
                             organ has a lower concentration
                             than the blood entering the organ.
                                The efficiency of Removal is
                              quantified by the Extraction Ratio
                                             [ER].
Extraction Ratio
  Extraction Ratio can be defined
as the proportion of drug removed
during passage through the organ.



   Ca
   Cv




                ������������ − ������������
         ������������ =
                    ������������
Clearance
                     A proportionality constant describing
                           the relationship between a
                         substance’s rate of elimination
                    (amount per unit time) at a given time
                     and its corresponding concentration
Clearance             in an appropriate fluid at that time.

    is:                      The hypothetical volume of blood
                                (plasma or serum) or other
                              biological fluids from which the
                               drug is totally and irreversibly
                                  removed per unit time.’

  Organ clearance = Blood flow rate X Extraction ratio
                     ������������ = ������. ������������
Hepatic
                                 Types of Clearance
  Clearance            Renal
                     Clearance

                                            The clearance of drug (a
         Metabolic                        fraction of total clearance)
         Clearance                        for a drug that is removed
                                                from the blood
   This is the total of every                 (plasma/serum) by
 individual organ clearances                  the process of renal
    that contribute to the                         excretion.
     elimination of drugs.
However, the organ clearance
    that can be routinely
determined independently in
  humans is renal clearance          ������������������������������������������ = ������������������������������������������ + ������������������������������ ������������������������������
because this is the only organ
   for which we can easily
  determine an elimination
              rate.
Clearance is a proportionality constant that relates rate
 of elimination (rate of excretion in renal clearance) to
   Plasma (or serum) concentration at any given time


              ������������������
                       ������ =   ������������������ ������������        ������
               ������������

               ������������
                       ������ =   ������������ ������������     ������
               ������������

                       ������������ = ������������
Elimination half-life
             vs. Clearance
                               0.693
     ������������ = ������������         ������½ =
                                 ������

                    0.693������
              ������½ =
                       ������������

 Elimination half life is dependent on the
volume of distribution and total clearance
Calculating Clearance

                                ������������������
     IV Bolus                              ������ =    ������������������ ������������      ������
                                 ������������

               Clearance for the entire dose can be
            obtained by integrating the right hand side
                 of the equation from t=0 to t=


            ������=∞   ������������
                          ������������     ������������������������������ ������������������������������������������������������������������ (������������������������)
                   ������������
������������ ������ =                      =
                    ������. ������������     ������������������������������ ������������������������ ������������������������������ ������ℎ������ ������������������������������
            ������=0
Calculating AUC
        IV Bolus
s




                 ������+������ ������
        Area =     2




          ������
                    ������




               ������
Calculating AUC
               Trapezoidal Rule:
                                C1 or concentration1
                                   C2 or concentration2




t1 or time1
                  t2 or time2
          Area = ((C1 + C2)/2)(t2 – t1)
������=∞                                  Calculating AUC
              ������. ������������           Trapezoidal Rule:
  ������=������
                                          C1 or concentration1
                                             C2 or concentration2




                          t1 or time1      t2 or time2
   ������=∞

              ������. ������������   = Area = Sum individual trapezoids
������=������������������������                     =(((C1 + C2)/2)(t2 – t1))
������=∞

        ������. ������������
                                      Calculating AUC
������=������              Trapezoidal Rule:

                                        C1 or concentration1
                                             C2 or concentration2

                                                                    ∞
                                                                ������������������������������������������




                                                                                 
         t1 or time1                      t2 or time2
        ������=∞
                          ������������������������ ������������������������������������������������������������������������������
                ������. ������������ =
    ������=������������������������
                                          ������
Creatinine Clearance
Creatinine clearance (Clcr) is renal clearance (Clr) applied
to endogenous creatinine ( a product of muscles
metabolism). It is used to monitor renal function and is a
valuable parameter for calculating dosage regimens in
elderly patients or those suffering from renal dysfunction.

Normal creatinine clearance (Clcr) values are:

• Adult males: 120±20mLmin-1
• Adult females: 108 ±20mLmin-1.
Creatinine Clearance
Direct measurement of Creatinine clearance



                              Rate of
              ∆������������          Creatinine
                             Excretion
               ∆������
������������������������   =
             (������������ )������������
                           Creatinine Serum
                            Concentration
Creatinine Clearance
                Indirect measurement of Creatinine clearance


Males:
                 ������������������������ℎ������(������������) × (140 − ������������������ )
    ������������������������   =
                       72 × ������������ ������������ (������������%)

Females:
                  ������������������������ℎ������(������������) × (140 − ������������������ )
������������������������   = 0.85
                        72 × ������������ ������������ (������������%)
Creatinine Clearance
            The significance of Creatinine clearance



1. Normal Creatinine clearance usually indicates normal
   kidney function
2. Creatinine clearance changes with age, physiological
   states, or other medical conditions and dose need to
   be changed accordingly
3. Dose frequency can be changed instead of changing
   the dos amount.
4. Changes in Creatinine clearance cause pharmacokinetic
   parameters to change.
Question 1
                    The table shows the concentration data vs
Time   Cp (ug/mL)
                    time for Cinoxacin after IV bolus
(hr)                administration. Plot the data and use the
                    graph to obtain the followings:
0.25   11.6±1.3
                    1. Elimination half-life (t½)
0.5    8.4±1.0      2. Elimination rate constant (k)
0.75   7.2±1.1      3. Apparent volume of distribution
1      6.1±1.1      4. Systemic clearance (Cls)
1.5    4.2±1.0      5. ∞������������������
                        0
2      3.2±0.9      6. Urine samples over 24 h showed the
                       percentage of the administered dose
3      1.9±0.7
                       recovered unchanged was 50.1%. The rest
4      1±0.4           were metablolites. Determine the renal
6      0.3±0.2         clearance (Clr), metabolic clearance (Clm),
8      0.09±0.1        the excretion rate constant (Ku), and the
                       metabolite rate constant (Km).
Plasma Concentration vs time
                                                    Rectilinear Paper
                               14




                               12
Plasma Concentration (ug/mL)




                               10




                                8




                                6




                                4




                                2




                                0
                                    0   1   2   3      4      5    6    7   8   9

                                                       Time (h)
Plasma Concentration vs time
                                                      Semilog Paper
                               100
Plasma Concentration (ug/mL)




                                                                                      t½=1.2h
                                10
                                                                                      K=0.577h-1
                                                                                      V=20.833L
                                                                                      Cls=12.02L/h
                                                                                      AUC=20.797u
                                 1                                                    g/mL
                                      0   1   2   3     4      5      6   7   8   9
                                                                                      Ku=0.298h-1
                                                                                      Km=0.287h-1


                                0.1




                               0.01
                                                        Time (h)
Pharmacokinetics

Anas Bahnassi PhD RPh
                           abahnassi@gmail.com

                      http://twitter.com/abahnassi

            http://www.linkedin.com/in/abahnassi

        http://www.udemy.com/pharmacokinetics

             http://www.slideshare.net/abahnassi

                  http://bahnassi.coursesites.com

        attribution – non-commercial – share alike

More Related Content

What's hot

Distribution of drugs
Distribution of drugsDistribution of drugs
Distribution of drugsViraj Shinde
 
ppt on pharmacokinetics pharmacolocy
ppt on pharmacokinetics pharmacolocy ppt on pharmacokinetics pharmacolocy
ppt on pharmacokinetics pharmacolocy AnuragSingh799
 
Methods to determine area under curve
Methods to determine area under curveMethods to determine area under curve
Methods to determine area under curveMd.Rakibul Islam
 
Absorption of drugs ,,,,,,,,
Absorption of drugs ,,,,,,,,Absorption of drugs ,,,,,,,,
Absorption of drugs ,,,,,,,,Viraj Shinde
 
Clearance Mechanism (Biopharmaceutics)
Clearance Mechanism (Biopharmaceutics)Clearance Mechanism (Biopharmaceutics)
Clearance Mechanism (Biopharmaceutics)HadeelSalah
 
Excretion of drugs and kinetics of elimination
Excretion of drugs and kinetics of eliminationExcretion of drugs and kinetics of elimination
Excretion of drugs and kinetics of eliminationhttp://neigrihms.gov.in/
 
Pharmacokinetics -Auc - area under curve
Pharmacokinetics -Auc -  area under curvePharmacokinetics -Auc -  area under curve
Pharmacokinetics -Auc - area under curveniravkd
 
Two compartment model
Two compartment modelTwo compartment model
Two compartment modelRooma Khalid
 
Drug distribution
Drug distributionDrug distribution
Drug distributionNaser Tadvi
 
One compartment model intro
One compartment model introOne compartment model intro
One compartment model introPankaj Nerkar
 
Basic pharmacokinetics and compartment modelling
Basic pharmacokinetics  and compartment modellingBasic pharmacokinetics  and compartment modelling
Basic pharmacokinetics and compartment modellingPriyankaDabirBharadk
 
Distribution of drugs Pharmacokinetics
Distribution of drugs PharmacokineticsDistribution of drugs Pharmacokinetics
Distribution of drugs PharmacokineticsJaineel Dharod
 
Factors affecting drug absorption
Factors affecting drug absorptionFactors affecting drug absorption
Factors affecting drug absorptionVarshaBarethiya
 
Drug transport across cell membrane.
Drug transport across cell membrane.Drug transport across cell membrane.
Drug transport across cell membrane.Dr. Salman H. Rizvi
 

What's hot (20)

Distribution of drugs
Distribution of drugsDistribution of drugs
Distribution of drugs
 
ppt on pharmacokinetics pharmacolocy
ppt on pharmacokinetics pharmacolocy ppt on pharmacokinetics pharmacolocy
ppt on pharmacokinetics pharmacolocy
 
Methods to determine area under curve
Methods to determine area under curveMethods to determine area under curve
Methods to determine area under curve
 
Absorption of drugs ,,,,,,,,
Absorption of drugs ,,,,,,,,Absorption of drugs ,,,,,,,,
Absorption of drugs ,,,,,,,,
 
Clearance Mechanism (Biopharmaceutics)
Clearance Mechanism (Biopharmaceutics)Clearance Mechanism (Biopharmaceutics)
Clearance Mechanism (Biopharmaceutics)
 
Excretion of drugs and kinetics of elimination
Excretion of drugs and kinetics of eliminationExcretion of drugs and kinetics of elimination
Excretion of drugs and kinetics of elimination
 
Pharmacokinetics -Auc - area under curve
Pharmacokinetics -Auc -  area under curvePharmacokinetics -Auc -  area under curve
Pharmacokinetics -Auc - area under curve
 
Two compartment model
Two compartment modelTwo compartment model
Two compartment model
 
Cytochrome p450
Cytochrome p450Cytochrome p450
Cytochrome p450
 
Excretion of drug (VK)
Excretion of drug (VK)Excretion of drug (VK)
Excretion of drug (VK)
 
Pharmacokinetics ppt
Pharmacokinetics pptPharmacokinetics ppt
Pharmacokinetics ppt
 
Pharmacokinetics
PharmacokineticsPharmacokinetics
Pharmacokinetics
 
Drug distribution
Drug distributionDrug distribution
Drug distribution
 
One compartment model intro
One compartment model introOne compartment model intro
One compartment model intro
 
Basic pharmacokinetics and compartment modelling
Basic pharmacokinetics  and compartment modellingBasic pharmacokinetics  and compartment modelling
Basic pharmacokinetics and compartment modelling
 
Distribution of drugs Pharmacokinetics
Distribution of drugs PharmacokineticsDistribution of drugs Pharmacokinetics
Distribution of drugs Pharmacokinetics
 
Factors affecting drug absorption
Factors affecting drug absorptionFactors affecting drug absorption
Factors affecting drug absorption
 
Basics of Pharmacokinetics
Basics of PharmacokineticsBasics of Pharmacokinetics
Basics of Pharmacokinetics
 
Drug transport across cell membrane.
Drug transport across cell membrane.Drug transport across cell membrane.
Drug transport across cell membrane.
 
Pharmacokinetic models
Pharmacokinetic modelsPharmacokinetic models
Pharmacokinetic models
 

Viewers also liked

Clinical pharmaco kinetics 1 bioavailability, 1st pass, renal clearance 2011
Clinical pharmaco kinetics 1 bioavailability, 1st pass, renal clearance 2011Clinical pharmaco kinetics 1 bioavailability, 1st pass, renal clearance 2011
Clinical pharmaco kinetics 1 bioavailability, 1st pass, renal clearance 2011Muhammad Saim
 
Clinical Pharmacokinetics-I [half life, order of kinetics, steady state]
Clinical Pharmacokinetics-I [half life, order of kinetics, steady state]Clinical Pharmacokinetics-I [half life, order of kinetics, steady state]
Clinical Pharmacokinetics-I [half life, order of kinetics, steady state]BADAR UDDIN UMAR
 
Concept of clearance & factors affecting renal excretion
Concept of clearance & factors affecting renal excretionConcept of clearance & factors affecting renal excretion
Concept of clearance & factors affecting renal excretionchiranjibi68
 
Compartment Modelling
Compartment ModellingCompartment Modelling
Compartment ModellingPallavi Kurra
 
Pharmacokinetics - drug absorption, drug distribution, drug metabolism, drug ...
Pharmacokinetics - drug absorption, drug distribution, drug metabolism, drug ...Pharmacokinetics - drug absorption, drug distribution, drug metabolism, drug ...
Pharmacokinetics - drug absorption, drug distribution, drug metabolism, drug ...http://neigrihms.gov.in/
 
Pharmacokinetics ppt
Pharmacokinetics pptPharmacokinetics ppt
Pharmacokinetics pptNITISH SHAH
 
Urine formation Plasma clearance by Dr. Riffat
Urine formation Plasma clearance by Dr. RiffatUrine formation Plasma clearance by Dr. Riffat
Urine formation Plasma clearance by Dr. RiffatSMS_2015
 
Pharmacokinetics II: Basic Concepts and Drug Clearance
Pharmacokinetics II: Basic Concepts and Drug ClearancePharmacokinetics II: Basic Concepts and Drug Clearance
Pharmacokinetics II: Basic Concepts and Drug ClearanceImhotep Virtual Medical School
 
Rules of integration
Rules of integrationRules of integration
Rules of integrationklawdet
 
Renal presentation
Renal presentationRenal presentation
Renal presentationTeketel23
 
Drug excretion
Drug excretionDrug excretion
Drug excretionSusie Ross
 

Viewers also liked (20)

Drug distribution & clearance
Drug distribution & clearanceDrug distribution & clearance
Drug distribution & clearance
 
Clinical pharmaco kinetics 1 bioavailability, 1st pass, renal clearance 2011
Clinical pharmaco kinetics 1 bioavailability, 1st pass, renal clearance 2011Clinical pharmaco kinetics 1 bioavailability, 1st pass, renal clearance 2011
Clinical pharmaco kinetics 1 bioavailability, 1st pass, renal clearance 2011
 
Clinical Pharmacokinetics-I [half life, order of kinetics, steady state]
Clinical Pharmacokinetics-I [half life, order of kinetics, steady state]Clinical Pharmacokinetics-I [half life, order of kinetics, steady state]
Clinical Pharmacokinetics-I [half life, order of kinetics, steady state]
 
Concept of clearance & factors affecting renal excretion
Concept of clearance & factors affecting renal excretionConcept of clearance & factors affecting renal excretion
Concept of clearance & factors affecting renal excretion
 
Pharmacokinetics: Lecture One
Pharmacokinetics: Lecture OnePharmacokinetics: Lecture One
Pharmacokinetics: Lecture One
 
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture twoPharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
 
Compartment Modelling
Compartment ModellingCompartment Modelling
Compartment Modelling
 
Pharmacokinetics
PharmacokineticsPharmacokinetics
Pharmacokinetics
 
Pharmacokinetics - drug absorption, drug distribution, drug metabolism, drug ...
Pharmacokinetics - drug absorption, drug distribution, drug metabolism, drug ...Pharmacokinetics - drug absorption, drug distribution, drug metabolism, drug ...
Pharmacokinetics - drug absorption, drug distribution, drug metabolism, drug ...
 
Pharmacokinetics ppt
Pharmacokinetics pptPharmacokinetics ppt
Pharmacokinetics ppt
 
Urine formation Plasma clearance by Dr. Riffat
Urine formation Plasma clearance by Dr. RiffatUrine formation Plasma clearance by Dr. Riffat
Urine formation Plasma clearance by Dr. Riffat
 
Pharmacokinetics II: Basic Concepts and Drug Clearance
Pharmacokinetics II: Basic Concepts and Drug ClearancePharmacokinetics II: Basic Concepts and Drug Clearance
Pharmacokinetics II: Basic Concepts and Drug Clearance
 
Rules of integration
Rules of integrationRules of integration
Rules of integration
 
Renal system 2
Renal system 2Renal system 2
Renal system 2
 
Integration Golden Rules
Integration Golden RulesIntegration Golden Rules
Integration Golden Rules
 
Renal presentation
Renal presentationRenal presentation
Renal presentation
 
Pharmacokinetics: Laboratory
Pharmacokinetics: LaboratoryPharmacokinetics: Laboratory
Pharmacokinetics: Laboratory
 
Pneumonia
PneumoniaPneumonia
Pneumonia
 
Renal Clearance
Renal ClearanceRenal Clearance
Renal Clearance
 
Drug excretion
Drug excretionDrug excretion
Drug excretion
 

Similar to Pharmacokinetics: Lecture Three

Aaditya- calculation of pk parameters
Aaditya- calculation of pk parametersAaditya- calculation of pk parameters
Aaditya- calculation of pk parametersAaditya Udupa
 
Pharmacokinetics
Pharmacokinetics Pharmacokinetics
Pharmacokinetics Umesh Yadav
 
one compartment open model
one compartment open modelone compartment open model
one compartment open modelSUJITHA MARY
 
ONE COMPARTMENT MODEL.pptx
ONE COMPARTMENT MODEL.pptxONE COMPARTMENT MODEL.pptx
ONE COMPARTMENT MODEL.pptxarti10aug
 
Pharmacokinetics of IV infusion, one-compartment open model
Pharmacokinetics of IV infusion, one-compartment open modelPharmacokinetics of IV infusion, one-compartment open model
Pharmacokinetics of IV infusion, one-compartment open modelAsuprita Patel
 
Compartment modeling
Compartment modelingCompartment modeling
Compartment modelingSHILPI BISWAS
 
สมการโคไค
สมการโคไคสมการโคไค
สมการโคไคAui Ounjai
 
39 pasko pcrrt drug dosing
39 pasko   pcrrt drug dosing39 pasko   pcrrt drug dosing
39 pasko pcrrt drug dosingDang Thanh Tuan
 
1 compartment model IV bolus administration equation
1 compartment model IV bolus administration equation1 compartment model IV bolus administration equation
1 compartment model IV bolus administration equationPrabhjot Singh Bajwa
 
one compartment open model
one compartment open model one compartment open model
one compartment open model NadiaSraboni
 
Continuous Renal Replacement Therapy
Continuous Renal Replacement TherapyContinuous Renal Replacement Therapy
Continuous Renal Replacement Therapyteja bayapalli
 
Week 4- the two open compartment
Week 4- the two open compartmentWeek 4- the two open compartment
Week 4- the two open compartmentlichlmh
 

Similar to Pharmacokinetics: Lecture Three (20)

Aaditya- calculation of pk parameters
Aaditya- calculation of pk parametersAaditya- calculation of pk parameters
Aaditya- calculation of pk parameters
 
Pharmacokinetics
Pharmacokinetics Pharmacokinetics
Pharmacokinetics
 
Pocket Guide: Pharmacokinetics Made Easy - sample
Pocket Guide: Pharmacokinetics Made Easy - sample Pocket Guide: Pharmacokinetics Made Easy - sample
Pocket Guide: Pharmacokinetics Made Easy - sample
 
one compartment open model
one compartment open modelone compartment open model
one compartment open model
 
Kinetika En 2002
Kinetika En 2002Kinetika En 2002
Kinetika En 2002
 
Kinetika En 2002
Kinetika En 2002Kinetika En 2002
Kinetika En 2002
 
ONE COMPARTMENT MODEL.pptx
ONE COMPARTMENT MODEL.pptxONE COMPARTMENT MODEL.pptx
ONE COMPARTMENT MODEL.pptx
 
Pharmacokinetics of IV infusion, one-compartment open model
Pharmacokinetics of IV infusion, one-compartment open modelPharmacokinetics of IV infusion, one-compartment open model
Pharmacokinetics of IV infusion, one-compartment open model
 
Compartment modeling
Compartment modelingCompartment modeling
Compartment modeling
 
Pharmacokinetics ppt
Pharmacokinetics pptPharmacokinetics ppt
Pharmacokinetics ppt
 
สมการโคไค
สมการโคไคสมการโคไค
สมการโคไค
 
Pharmacocinetic
PharmacocineticPharmacocinetic
Pharmacocinetic
 
2.pharmacokinetics
2.pharmacokinetics2.pharmacokinetics
2.pharmacokinetics
 
39 pasko pcrrt drug dosing
39 pasko   pcrrt drug dosing39 pasko   pcrrt drug dosing
39 pasko pcrrt drug dosing
 
1 compartment model IV bolus administration equation
1 compartment model IV bolus administration equation1 compartment model IV bolus administration equation
1 compartment model IV bolus administration equation
 
one compartment open model
one compartment open model one compartment open model
one compartment open model
 
Continuous Renal Replacement Therapy
Continuous Renal Replacement TherapyContinuous Renal Replacement Therapy
Continuous Renal Replacement Therapy
 
Elementary pharmacokinetics jap
Elementary pharmacokinetics japElementary pharmacokinetics jap
Elementary pharmacokinetics jap
 
TOXICOKINETICS
TOXICOKINETICSTOXICOKINETICS
TOXICOKINETICS
 
Week 4- the two open compartment
Week 4- the two open compartmentWeek 4- the two open compartment
Week 4- the two open compartment
 

More from Anas Bahnassi أنس البهنسي

Pharmacy Practice: Lecture one: Medication Management Cycle Part One
Pharmacy Practice: Lecture one: Medication Management Cycle Part OnePharmacy Practice: Lecture one: Medication Management Cycle Part One
Pharmacy Practice: Lecture one: Medication Management Cycle Part OneAnas Bahnassi أنس البهنسي
 

More from Anas Bahnassi أنس البهنسي (20)

Lecture nine cardiovascular_emeregencies
Lecture nine cardiovascular_emeregenciesLecture nine cardiovascular_emeregencies
Lecture nine cardiovascular_emeregencies
 
Urinary Tract Infections
Urinary Tract InfectionsUrinary Tract Infections
Urinary Tract Infections
 
Influenza
InfluenzaInfluenza
Influenza
 
Acute bronchitis
Acute bronchitisAcute bronchitis
Acute bronchitis
 
Sinusitis
SinusitisSinusitis
Sinusitis
 
Streptococccal sore throat
Streptococccal sore throatStreptococccal sore throat
Streptococccal sore throat
 
Acute Otitis Media
Acute Otitis Media Acute Otitis Media
Acute Otitis Media
 
Principles of infectious diseases
Principles of infectious diseasesPrinciples of infectious diseases
Principles of infectious diseases
 
Lecture three management cycle Part 3
Lecture three management cycle Part 3Lecture three management cycle Part 3
Lecture three management cycle Part 3
 
Lecture two management cycle Part: 2
Lecture two management cycle Part: 2Lecture two management cycle Part: 2
Lecture two management cycle Part: 2
 
Pharmacy Practice: Lecture one: Medication Management Cycle Part One
Pharmacy Practice: Lecture one: Medication Management Cycle Part OnePharmacy Practice: Lecture one: Medication Management Cycle Part One
Pharmacy Practice: Lecture one: Medication Management Cycle Part One
 
Osteoarthritis
OsteoarthritisOsteoarthritis
Osteoarthritis
 
Juvenile idiopathic arthritis
Juvenile idiopathic arthritisJuvenile idiopathic arthritis
Juvenile idiopathic arthritis
 
Rheumatoid arthritis Part 2
Rheumatoid arthritis Part 2Rheumatoid arthritis Part 2
Rheumatoid arthritis Part 2
 
Rheumatoid Arthritis Part !
Rheumatoid Arthritis Part !Rheumatoid Arthritis Part !
Rheumatoid Arthritis Part !
 
Pharmacotherapy of Diabetes: Part 2
Pharmacotherapy of Diabetes: Part 2Pharmacotherapy of Diabetes: Part 2
Pharmacotherapy of Diabetes: Part 2
 
Role of community pharmacists in diabetes management
Role of community pharmacists in diabetes managementRole of community pharmacists in diabetes management
Role of community pharmacists in diabetes management
 
Diabetes Care: Part One
Diabetes Care: Part OneDiabetes Care: Part One
Diabetes Care: Part One
 
Premixed insulin dosing in actual practice
Premixed insulin dosing in actual practicePremixed insulin dosing in actual practice
Premixed insulin dosing in actual practice
 
A quick review of available insulin products
A quick review of available insulin productsA quick review of available insulin products
A quick review of available insulin products
 

Recently uploaded

Interactive Powerpoint_How to Master effective communication
Interactive Powerpoint_How to Master effective communicationInteractive Powerpoint_How to Master effective communication
Interactive Powerpoint_How to Master effective communicationnomboosow
 
_Math 4-Q4 Week 5.pptx Steps in Collecting Data
_Math 4-Q4 Week 5.pptx Steps in Collecting Data_Math 4-Q4 Week 5.pptx Steps in Collecting Data
_Math 4-Q4 Week 5.pptx Steps in Collecting DataJhengPantaleon
 
call girls in Kamla Market (DELHI) 🔝 >༒9953330565🔝 genuine Escort Service 🔝✔️✔️
call girls in Kamla Market (DELHI) 🔝 >༒9953330565🔝 genuine Escort Service 🔝✔️✔️call girls in Kamla Market (DELHI) 🔝 >༒9953330565🔝 genuine Escort Service 🔝✔️✔️
call girls in Kamla Market (DELHI) 🔝 >༒9953330565🔝 genuine Escort Service 🔝✔️✔️9953056974 Low Rate Call Girls In Saket, Delhi NCR
 
Paris 2024 Olympic Geographies - an activity
Paris 2024 Olympic Geographies - an activityParis 2024 Olympic Geographies - an activity
Paris 2024 Olympic Geographies - an activityGeoBlogs
 
URLs and Routing in the Odoo 17 Website App
URLs and Routing in the Odoo 17 Website AppURLs and Routing in the Odoo 17 Website App
URLs and Routing in the Odoo 17 Website AppCeline George
 
Class 11 Legal Studies Ch-1 Concept of State .pdf
Class 11 Legal Studies Ch-1 Concept of State .pdfClass 11 Legal Studies Ch-1 Concept of State .pdf
Class 11 Legal Studies Ch-1 Concept of State .pdfakmcokerachita
 
Incoming and Outgoing Shipments in 1 STEP Using Odoo 17
Incoming and Outgoing Shipments in 1 STEP Using Odoo 17Incoming and Outgoing Shipments in 1 STEP Using Odoo 17
Incoming and Outgoing Shipments in 1 STEP Using Odoo 17Celine George
 
microwave assisted reaction. General introduction
microwave assisted reaction. General introductionmicrowave assisted reaction. General introduction
microwave assisted reaction. General introductionMaksud Ahmed
 
How to Configure Email Server in Odoo 17
How to Configure Email Server in Odoo 17How to Configure Email Server in Odoo 17
How to Configure Email Server in Odoo 17Celine George
 
Organic Name Reactions for the students and aspirants of Chemistry12th.pptx
Organic Name Reactions  for the students and aspirants of Chemistry12th.pptxOrganic Name Reactions  for the students and aspirants of Chemistry12th.pptx
Organic Name Reactions for the students and aspirants of Chemistry12th.pptxVS Mahajan Coaching Centre
 
Enzyme, Pharmaceutical Aids, Miscellaneous Last Part of Chapter no 5th.pdf
Enzyme, Pharmaceutical Aids, Miscellaneous Last Part of Chapter no 5th.pdfEnzyme, Pharmaceutical Aids, Miscellaneous Last Part of Chapter no 5th.pdf
Enzyme, Pharmaceutical Aids, Miscellaneous Last Part of Chapter no 5th.pdfSumit Tiwari
 
Science 7 - LAND and SEA BREEZE and its Characteristics
Science 7 - LAND and SEA BREEZE and its CharacteristicsScience 7 - LAND and SEA BREEZE and its Characteristics
Science 7 - LAND and SEA BREEZE and its CharacteristicsKarinaGenton
 
POINT- BIOCHEMISTRY SEM 2 ENZYMES UNIT 5.pptx
POINT- BIOCHEMISTRY SEM 2 ENZYMES UNIT 5.pptxPOINT- BIOCHEMISTRY SEM 2 ENZYMES UNIT 5.pptx
POINT- BIOCHEMISTRY SEM 2 ENZYMES UNIT 5.pptxSayali Powar
 
Call Girls in Dwarka Mor Delhi Contact Us 9654467111
Call Girls in Dwarka Mor Delhi Contact Us 9654467111Call Girls in Dwarka Mor Delhi Contact Us 9654467111
Call Girls in Dwarka Mor Delhi Contact Us 9654467111Sapana Sha
 
Solving Puzzles Benefits Everyone (English).pptx
Solving Puzzles Benefits Everyone (English).pptxSolving Puzzles Benefits Everyone (English).pptx
Solving Puzzles Benefits Everyone (English).pptxOH TEIK BIN
 
The basics of sentences session 2pptx copy.pptx
The basics of sentences session 2pptx copy.pptxThe basics of sentences session 2pptx copy.pptx
The basics of sentences session 2pptx copy.pptxheathfieldcps1
 
Software Engineering Methodologies (overview)
Software Engineering Methodologies (overview)Software Engineering Methodologies (overview)
Software Engineering Methodologies (overview)eniolaolutunde
 

Recently uploaded (20)

Interactive Powerpoint_How to Master effective communication
Interactive Powerpoint_How to Master effective communicationInteractive Powerpoint_How to Master effective communication
Interactive Powerpoint_How to Master effective communication
 
_Math 4-Q4 Week 5.pptx Steps in Collecting Data
_Math 4-Q4 Week 5.pptx Steps in Collecting Data_Math 4-Q4 Week 5.pptx Steps in Collecting Data
_Math 4-Q4 Week 5.pptx Steps in Collecting Data
 
call girls in Kamla Market (DELHI) 🔝 >༒9953330565🔝 genuine Escort Service 🔝✔️✔️
call girls in Kamla Market (DELHI) 🔝 >༒9953330565🔝 genuine Escort Service 🔝✔️✔️call girls in Kamla Market (DELHI) 🔝 >༒9953330565🔝 genuine Escort Service 🔝✔️✔️
call girls in Kamla Market (DELHI) 🔝 >༒9953330565🔝 genuine Escort Service 🔝✔️✔️
 
Paris 2024 Olympic Geographies - an activity
Paris 2024 Olympic Geographies - an activityParis 2024 Olympic Geographies - an activity
Paris 2024 Olympic Geographies - an activity
 
URLs and Routing in the Odoo 17 Website App
URLs and Routing in the Odoo 17 Website AppURLs and Routing in the Odoo 17 Website App
URLs and Routing in the Odoo 17 Website App
 
Class 11 Legal Studies Ch-1 Concept of State .pdf
Class 11 Legal Studies Ch-1 Concept of State .pdfClass 11 Legal Studies Ch-1 Concept of State .pdf
Class 11 Legal Studies Ch-1 Concept of State .pdf
 
Incoming and Outgoing Shipments in 1 STEP Using Odoo 17
Incoming and Outgoing Shipments in 1 STEP Using Odoo 17Incoming and Outgoing Shipments in 1 STEP Using Odoo 17
Incoming and Outgoing Shipments in 1 STEP Using Odoo 17
 
microwave assisted reaction. General introduction
microwave assisted reaction. General introductionmicrowave assisted reaction. General introduction
microwave assisted reaction. General introduction
 
How to Configure Email Server in Odoo 17
How to Configure Email Server in Odoo 17How to Configure Email Server in Odoo 17
How to Configure Email Server in Odoo 17
 
Organic Name Reactions for the students and aspirants of Chemistry12th.pptx
Organic Name Reactions  for the students and aspirants of Chemistry12th.pptxOrganic Name Reactions  for the students and aspirants of Chemistry12th.pptx
Organic Name Reactions for the students and aspirants of Chemistry12th.pptx
 
Enzyme, Pharmaceutical Aids, Miscellaneous Last Part of Chapter no 5th.pdf
Enzyme, Pharmaceutical Aids, Miscellaneous Last Part of Chapter no 5th.pdfEnzyme, Pharmaceutical Aids, Miscellaneous Last Part of Chapter no 5th.pdf
Enzyme, Pharmaceutical Aids, Miscellaneous Last Part of Chapter no 5th.pdf
 
Model Call Girl in Tilak Nagar Delhi reach out to us at 🔝9953056974🔝
Model Call Girl in Tilak Nagar Delhi reach out to us at 🔝9953056974🔝Model Call Girl in Tilak Nagar Delhi reach out to us at 🔝9953056974🔝
Model Call Girl in Tilak Nagar Delhi reach out to us at 🔝9953056974🔝
 
Science 7 - LAND and SEA BREEZE and its Characteristics
Science 7 - LAND and SEA BREEZE and its CharacteristicsScience 7 - LAND and SEA BREEZE and its Characteristics
Science 7 - LAND and SEA BREEZE and its Characteristics
 
POINT- BIOCHEMISTRY SEM 2 ENZYMES UNIT 5.pptx
POINT- BIOCHEMISTRY SEM 2 ENZYMES UNIT 5.pptxPOINT- BIOCHEMISTRY SEM 2 ENZYMES UNIT 5.pptx
POINT- BIOCHEMISTRY SEM 2 ENZYMES UNIT 5.pptx
 
Call Girls in Dwarka Mor Delhi Contact Us 9654467111
Call Girls in Dwarka Mor Delhi Contact Us 9654467111Call Girls in Dwarka Mor Delhi Contact Us 9654467111
Call Girls in Dwarka Mor Delhi Contact Us 9654467111
 
Solving Puzzles Benefits Everyone (English).pptx
Solving Puzzles Benefits Everyone (English).pptxSolving Puzzles Benefits Everyone (English).pptx
Solving Puzzles Benefits Everyone (English).pptx
 
The basics of sentences session 2pptx copy.pptx
The basics of sentences session 2pptx copy.pptxThe basics of sentences session 2pptx copy.pptx
The basics of sentences session 2pptx copy.pptx
 
Staff of Color (SOC) Retention Efforts DDSD
Staff of Color (SOC) Retention Efforts DDSDStaff of Color (SOC) Retention Efforts DDSD
Staff of Color (SOC) Retention Efforts DDSD
 
Software Engineering Methodologies (overview)
Software Engineering Methodologies (overview)Software Engineering Methodologies (overview)
Software Engineering Methodologies (overview)
 
Código Creativo y Arte de Software | Unidad 1
Código Creativo y Arte de Software | Unidad 1Código Creativo y Arte de Software | Unidad 1
Código Creativo y Arte de Software | Unidad 1
 

Pharmacokinetics: Lecture Three

  • 1. Clearance Concept Anas Bahnassi PhD RPh
  • 2. Lecture Objectives After the completion of this lecture the student should be able to: 1. Define clearance and extraction ratio and describe the relationship between them. 2. Distinguish clearance from elimination rate and elimination rate constant. 3. Explain the dependence of elimination half life on apparent volume of distribution and clearance 4. Calculate area under the plasma drug concentration versus time curve by use of the trapezoidal rule and by other methods 5. Calculate a patient’s creatinine clearance using the appropriate equation 6. Calculate dosing adjustments of a renally excreted drug in patients with various degrees of renal impairment (dysfunction).
  • 3. A Physiological Approach to Understand Clearance Concept Site of Action Heart Clearing Organ (Pump) (Kidney/Liver) The blood exiting the eliminating organ has a lower concentration than the blood entering the organ. The efficiency of Removal is quantified by the Extraction Ratio [ER].
  • 4. Extraction Ratio Extraction Ratio can be defined as the proportion of drug removed during passage through the organ. Ca Cv ������������ − ������������ ������������ = ������������
  • 5. Clearance A proportionality constant describing the relationship between a substance’s rate of elimination (amount per unit time) at a given time and its corresponding concentration Clearance in an appropriate fluid at that time. is: The hypothetical volume of blood (plasma or serum) or other biological fluids from which the drug is totally and irreversibly removed per unit time.’ Organ clearance = Blood flow rate X Extraction ratio ������������ = ������. ������������
  • 6. Hepatic Types of Clearance Clearance Renal Clearance The clearance of drug (a Metabolic fraction of total clearance) Clearance for a drug that is removed from the blood This is the total of every (plasma/serum) by individual organ clearances the process of renal that contribute to the excretion. elimination of drugs. However, the organ clearance that can be routinely determined independently in humans is renal clearance ������������������������������������������ = ������������������������������������������ + ������������������������������ ������������������������������ because this is the only organ for which we can easily determine an elimination rate.
  • 7. Clearance is a proportionality constant that relates rate of elimination (rate of excretion in renal clearance) to Plasma (or serum) concentration at any given time ������������������ ������ = ������������������ ������������ ������ ������������ ������������ ������ = ������������ ������������ ������ ������������ ������������ = ������������
  • 8. Elimination half-life vs. Clearance 0.693 ������������ = ������������ ������½ = ������ 0.693������ ������½ = ������������ Elimination half life is dependent on the volume of distribution and total clearance
  • 9. Calculating Clearance ������������������ IV Bolus ������ = ������������������ ������������ ������ ������������ Clearance for the entire dose can be obtained by integrating the right hand side of the equation from t=0 to t= ������=∞ ������������ ������������ ������������������������������ ������������������������������������������������������������������ (������������������������) ������������ ������������ ������ = = ������. ������������ ������������������������������ ������������������������ ������������������������������ ������ℎ������ ������������������������������ ������=0
  • 10. Calculating AUC IV Bolus s ������+������ ������ Area = 2 ������ ������ ������
  • 11. Calculating AUC Trapezoidal Rule: C1 or concentration1 C2 or concentration2 t1 or time1 t2 or time2 Area = ((C1 + C2)/2)(t2 – t1)
  • 12. ������=∞ Calculating AUC ������. ������������ Trapezoidal Rule: ������=������ C1 or concentration1 C2 or concentration2 t1 or time1 t2 or time2 ������=∞ ������. ������������ = Area = Sum individual trapezoids ������=������������������������ =(((C1 + C2)/2)(t2 – t1))
  • 13. ������=∞ ������. ������������ Calculating AUC ������=������ Trapezoidal Rule: C1 or concentration1 C2 or concentration2 ∞ ������������������������������������������  t1 or time1 t2 or time2 ������=∞ ������������������������ ������������������������������������������������������������������������������ ������. ������������ = ������=������������������������ ������
  • 14. Creatinine Clearance Creatinine clearance (Clcr) is renal clearance (Clr) applied to endogenous creatinine ( a product of muscles metabolism). It is used to monitor renal function and is a valuable parameter for calculating dosage regimens in elderly patients or those suffering from renal dysfunction. Normal creatinine clearance (Clcr) values are: • Adult males: 120±20mLmin-1 • Adult females: 108 ±20mLmin-1.
  • 15. Creatinine Clearance Direct measurement of Creatinine clearance Rate of ∆������������ Creatinine Excretion ∆������ ������������������������ = (������������ )������������ Creatinine Serum Concentration
  • 16. Creatinine Clearance Indirect measurement of Creatinine clearance Males: ������������������������ℎ������(������������) × (140 − ������������������ ) ������������������������ = 72 × ������������ ������������ (������������%) Females: ������������������������ℎ������(������������) × (140 − ������������������ ) ������������������������ = 0.85 72 × ������������ ������������ (������������%)
  • 17. Creatinine Clearance The significance of Creatinine clearance 1. Normal Creatinine clearance usually indicates normal kidney function 2. Creatinine clearance changes with age, physiological states, or other medical conditions and dose need to be changed accordingly 3. Dose frequency can be changed instead of changing the dos amount. 4. Changes in Creatinine clearance cause pharmacokinetic parameters to change.
  • 18. Question 1 The table shows the concentration data vs Time Cp (ug/mL) time for Cinoxacin after IV bolus (hr) administration. Plot the data and use the graph to obtain the followings: 0.25 11.6±1.3 1. Elimination half-life (t½) 0.5 8.4±1.0 2. Elimination rate constant (k) 0.75 7.2±1.1 3. Apparent volume of distribution 1 6.1±1.1 4. Systemic clearance (Cls) 1.5 4.2±1.0 5. ∞������������������ 0 2 3.2±0.9 6. Urine samples over 24 h showed the percentage of the administered dose 3 1.9±0.7 recovered unchanged was 50.1%. The rest 4 1±0.4 were metablolites. Determine the renal 6 0.3±0.2 clearance (Clr), metabolic clearance (Clm), 8 0.09±0.1 the excretion rate constant (Ku), and the metabolite rate constant (Km).
  • 19. Plasma Concentration vs time Rectilinear Paper 14 12 Plasma Concentration (ug/mL) 10 8 6 4 2 0 0 1 2 3 4 5 6 7 8 9 Time (h)
  • 20. Plasma Concentration vs time Semilog Paper 100 Plasma Concentration (ug/mL) t½=1.2h 10 K=0.577h-1 V=20.833L Cls=12.02L/h AUC=20.797u 1 g/mL 0 1 2 3 4 5 6 7 8 9 Ku=0.298h-1 Km=0.287h-1 0.1 0.01 Time (h)
  • 21. Pharmacokinetics Anas Bahnassi PhD RPh abahnassi@gmail.com http://twitter.com/abahnassi http://www.linkedin.com/in/abahnassi http://www.udemy.com/pharmacokinetics http://www.slideshare.net/abahnassi http://bahnassi.coursesites.com attribution – non-commercial – share alike