[1] The document discusses basic pharmacokinetic concepts including bioavailability, volume of distribution, and elimination kinetics. [2] Bioavailability refers to the extent of absorption of an administered dose and is expressed as a percentage or fraction relative to intravenous administration. It depends on factors like absorption, first-pass metabolism, and solubility. [3] Volume of distribution is a theoretical volume in which an administered dose would be distributed if concentrations were uniform throughout body water compartments. It is calculated based on plasma concentration and the administered dose. [4] Drugs can follow first-order or zero-order elimination kinetics. First-order kinetics involve a fixed fraction eliminated per unit time while zero-order

1. Basic Concepts of Pharmacokinetic
Dr. Anoop Kumar
Assistant Professor
NIPER-R
IV Drug
Distribution
[α] Phase
Elimination
[β] Phase
0 4 8 12 16 20 24 28 32 36
TIME (HOURS)
LOG-PLASMA CONCENTRATION vs. TIME PLOT
16
2
8
4
1
64
32

2. 2
Modern Look
Pharmaco-kinetics
set-up

3. CLINICAL PHARMACOKINETICS
 PHARMACOTHERAPY aims at a therapy
that is –
EFFECTIVE
SAFE
INDIVIDUALIZED
(for each patient’s need)
AFFORDABLE
RATIONAL (not Irrational)
 Successful Therapy depends on the
“TISSUE-RESPONSE to the Drug”
SELECTIVE
3

4. CLINICAL PHARMACOKINETICS
HIGHER the DOSE MORE the EFFECT
NO

?? DIRECTLY
PROPORTIONAL
%
R
E
S
P
O
N
S
E
D O S E
RESPONSE is
PROPORTIONAL
to Log-DOSE

Log-D O S E
%
R
E
S
P
O
N
S
E
%
R
E
S
P
O
N
S
E
D O S E
ACTUALLY
IT IS
4
TISSUE RESPONSE
(Therapeutic Effect)
DOSE DEPENDENT

5. CLINICAL PHARMACOKINETICS
 HELPS US TO -
UNDERSTAND THE QUANTITATIVE
RELATIONSHIP BETWEEN THE DOSE &
CLINICAL EFFECT
& thereby
 PREDICT THE PATIENT’S RESPONSE TO
A GIVEN DOSE IN THE LIGHT OF THE
“SPECIFIC FACTORS IN THAT PATIENT”
 PURPOSE:- INDIVIDUALIZE & OPTIMIZE
THE TREATMENT for that patient 5

6. CLINICAL PHARMACOKINETICS
 RESPONSE DEPENDS ON “TARGET TISSUE
CONCENTRATION” OF DRUG
 CAN DRUG CONCENTRATION BE EASILY
MONITORED IN “TARGET TISSUES”?
e.g. in Heart, Brain ??
NO!!!!
 WHAT IS THE NEXT BEST OPTION??
6

7. CLINICAL PHARMACOKINETICS
TARGET TISSUE CONCENTRATION
BLOOD / PLASMA CONCENTRATION
(which is easily monitored)
DRUG’S PLASMA
CONCENTRATION
DEPEND ON ???
IS IN EQUILIBRIUM WITH
7

8. BLOOD / PLASMA CONCENTRATION DEPENDS ON
2. HOW DRUG
DISTRIBUTES to
Different Body
Compartments
3. HOW DOES
DRUG GET
ELIMINATED
from Body
1. HOW MUCH
DRUG reaches
Blood from sites
of administration
8

9. BLOOD / PLASMA CONCENTRATION DEPENDS ON
DISTRIBUTION
• Volume of
Distribution (Vd)
• Barriers
ELIMINATION
•HALF LIFE
Biotransformation
Excretion
ABSORPTION
•Bioavailability
•Dose
DRUG
9

10. ∴ Plasma Concentration Depends on 3 factors -
2.
Volume of
Distribution (Vd)
3.
HALF LIFE (T ½ )
1.
Bioavailability
10

11. 11
1.
BIOAVAILABILITY
[ F ]

12. 1. BIOAVAILABILITY (F)
 THE EXTENT (& RATE) TO WHICH THE
ADMINISTERED DOSE IS AVAILABLE
IN BLOOD IN UNCHANGED FORM (i.e.
available for action in target tissues)
 EXPRESSED AS % OR FRACTION (F)
 I.V. DOSE - BY DEFINITION ASSUMED
TO BE 100% BIOAVAILABLE (F = 1)
 ‘F’ BY OTHER ROUTES EXPRESSED
RELATIVE TO I.V. BIOAVAILABILITY
12

13. PLASMACONCENTRATIONOFDRUG
TIME
DRUG ADMINISTERED
I.V. DRUG
ORAL DRUG
AUC Oral
AUC i.v.
AUC Oral
BIOAVAILABILITY = -------------- x 100
(ORAL) AUC i.v.
i.e. EXPRESSED AS % of I.V.,
which is assumed to be 100 %
OR as Fraction “F” (of I.V.)
 “30% (or 0.3)” means that 70%
(or 0.7 fraction) not absorbed
&/or destroyed in GIT/Liver
before reaching systemic
circulation
13AUC = AREA UNDER CURVE

14. AUC Oral
BIOAVAILABILITY = -------------------- X 100
AUC i.v.
Calculated by TRAPEZOID METHOD
Area = Width x (Σ Unequal lengths  2)
TRAPEZOIDS
OF Oral AUC
TRAPEZOIDS
OF i.v. AUC
PLASMACONCENTRATIONOFDRUG
TIME
DRUG ADMINISTERED
AUC Oral
AUC i.v.
14
AUC can
also be
calculated
by other
methods

15. ROUTE ‘F’ % CHARACTERISTICS
I.V. 100 Fastest onset of action
V. Large volume can be given
I.M. 75 - ≤100 Moderate volume injectable
Painful injection
S.C. 75 - ≤100 Smaller volume than I.M.
Painful injection
ORAL 05 - <100 Most convenient
High First Pass Metabolism
P.R. 30 - <100 Inconvenient
Less First Pass Metabolism
INHALA-
TION 05 - <100 Very Rapid Action
TRANS-
DERMAL 80 - <100
Very Slow Absorption
SUSTAINED Action
No First Pass metabolism 15

16. ‘TWO’ VARIABLES AFFECT BIOAVAILABILITY
1.VARIATIONS IN
DRUG
ABSORPTION
2. VARIATIONS IN
DRUG
METABOLISM
16

17. ‘TWO’ VARIABLES AFFECT BIOAVAILABILITY
1.VARIATIONS IN
DRUG
ABSORPTION
A. Variations in
DISINTEGRATION
TIME of Solids
B. Variations in
DISSOLUTION
TIME of Solids
17
C. SOLUBILITY
of drug
D. STABILITY
of drug

18. FACTORS AFFECTING BIOAVAILABILITY-
1. VARIATIONS IN ABSORPTION due to:
A. DISINTEGRATION TIME of Solids (Tablet) may
differ due to Variations in –
• COMPRESSION FORCE &
• BINDING MATERIAL used in preparing Tablets
B. DISSOLUTION TIME of drug Particles
(after Disintegration) can Vary due to –
• PARTICLE SIZE
• PHYSICAL FORM - CRYSTALLINE/ AMORPHOUS
☞ THEREFORE POORLY SOLUBLE DRUGS –
(e.g. Griseofulvin, Spironolactone , Aspirin)
 ABSORBED FASTER & BETTER
in MICROFINED FORM

19. FACTORS AFFECTING BIOAVAILABILITY-
1. VARIATIONS IN ABSORPTION - contd
C. DRUG SOLUBILITY
• VERY HYDROPHILIC drugs are poorly absorbed
as they can not cross lipid-rich cell membranes
• EXTREMELY HYDROPHOBIC drugs also do not
cross cell membranes as they need to have
some water solubility to diffuse in water medium
on two sides of the cell membranes
B. CHEMICAL STABILITY of drug to -
• ACID pH of Stomach (e.g. Penicillin G vs
Amoxilcillin)
• GUT ENZYMES - e.g. Insulin destroyed by GIT
enzymes

20. WHY VARIATIONS IN BIOAVAILABILITY ?
2. VARIATIONS IN DRUG METABOLISM:
PRE-SYSTEMIC Metabolism
• Mainly HEPATIC 1st Pass metabolism
(& Hepatic Excretion into bile)
• GIT Digestive Juices/Tissues (Minor)
SOME Ex. OF ORAL BIOAVAILABILITY (%)
Amoxicillin 93 Digoxin 70
Ampicillin 62 Digitoxin 90
Aspirin 68 Propranolol 26
Indomethacin 98 Atenolol 56
Morphine 24 Phenytoin 90
Pethidine 52 Carbamazepine 70
Phenobarbitone 100 20

21. BIOAVAILABILITY -contd
BIOEQUIVALENCE: is an important clinical
issue BECAUSE-
• SEVERAL BRANDED & GENERIC DRUG
PREPARATIONS FROM MANY DRUG
COMPANIES are available in market
• Only “BIOEQUIVALENT” PREPARATIONS
are INTER-CHANGEABLE for the Patient
• Also, DIFFERENT BATCHES OF ‘A DRUG’
made by ‘SAME COMPANY’ should always
be BIOEQUIVALENT.
• But even they are Not Always Bioequivalent
21

22. BIOAVAILABILITY -contd
TWO SAMPLES ARE SAID TO BE
BIOEQUIVALENT only when they show-
Comparable Area Under Curve (AUC) i.e.
same ‘F’ (Fraction or Bioavailability) &
Similar Time to reach Peak Plasma Conc.
(T-max)
*AUC reflects EXTENT of absorption, &
*T-max reflects RATE of absorption
Otherwise the TWO SAMPLES
are Bio-inequivalent
RATE of Absorption, & both MUST
EXTENT of Absorption BE SIMILAR
22

23. B
A
PLASMACONCENTRATIONOFDRUG
TIMEDRUG
THERAPEUTIC
RANGE
TOXIC
RANGE
SUB-
CLINICAL
Tmax
A&B
Tmax
C
C
23
ALL 3 SAMPLES are
BIO-INEQUIVALENT
Tmax AC;
But ‘F’ A≃C
Tmax A=B;
But ‘F’ B<A

24. A = Brand A
B1= Brand B, Batch 1
B1= Brand B, Batch 2
B2
A
B1
SERUMDIGOXINCONC.
(ng/ml)
012
0 1 2 3 4 5 6
TIME (hr)
• AUC in 3 Samples Varies from 80% to 40%
• For Drugs which have T.I. <2.5 & ‘F’ > 95%
 A Change to another BRAND,
or to a Poorer Quality Tablet
can cause TOXICITY, or
Therapeutic Failure 24
3 Lots of Digoxin
Tablets (oral 0.5 mg)

25. BIOAVAILABILITY -contd
BIO-INEQUIVALENCE: can cause following
Clinical Consequences-
• DRUGS WITH NARROW THERAPEUTIC
INDEX 
OVERDOSAGE Toxicity if “F” is Higher
than expected (e.g. Digoxin, Phenytoin)
• CRUCIAL LIFE SAVING DRUGS 
THERAPEUTIC FAILURE if “F” is Lower
than expected (e.g. Antimicrobials,
Antiasthmatics)
• HIGHER DOSE NEEDED if “F” is Lower than
expected
25

26. 26
2.
VOLUME
OF
DISTRIBUTION
[ Vd , AVd]

27. 2. Volume of Distribution (AVd)
 MOST ADMINISTERED DRUG TEND TO
DISTRIBUTE MAINLY IN BODY WATER
(SOME DRUGS PREFERENTIALLY
LOCALISE IN LIPIDS)
 BODY WATER CAN BE VIEWED AS BEING
LOCATED IN “COMPARTMENTS”
 ACCORDINGLY DIFFERENT DRUGS MAY
BE DISTRIBUTED IN DIFFERENT WATER-
COMPARTMENTS
27

28. EXTRACELLULAR
WATER
14 L
10 L 4 L
Interstitial
Volume
Plasma
Volume
Total Body H2O (60%)* 42L
Extra-cellular (20%)* 14L
-Interstitial (14%)* 10L
-Plasma Vol. (06%)* 04L
Intra-cellular (40%)* 28L
(* % of B Wt)
INTRACELLULAR
WATER
28 L
42 Liters
TOTAL BODY WATER
Plasma
Interstitial
Volume
Intracellular
Volume

29. Volume of Distribution (AVd)
 “THEORETICAL” (APPARENT) VOLUME OF
BODY WATER IN WHICH A GIVEN DOSE
WILL BE ACCOMMODATED “IF THE DRUG
CONCENTRATION EVERYWHERE IS SAME
AS IN PLASMA (i.e. Uniformly Distributed)”
 EXPRESSED AS Liters for a 70 kg adult
(or as mL / kg body weight)
 Vd = DoseConcentration in Plasma (D  C)
 Example: 25 mg dose  1 mg/L = 25 L
29

30. Volume of Distribution (AVd)
 Vd = Dose  Concentration in Plasma (D  C)
ASSUMES THAT the given Dose –
Stays in body (i.e. Not Eliminated)
& Distributes ‘INSTANTLY’ to DIFFERENT
COMPARTMENTS & Reach EQUILIBRIUM
 IN REALITY: This does not happen, because -
Elimination Starts Instantly &
Equilibrium takes some time to reach
 to Find Vd Correctly – we need to know
(a) C0 [Plasma Conc. At time ‘0’ (Zero)]
(Before Elimination & Equilibring starts)
& (b) Type of Elimination kinetics of that drug30

31. TYPES OF ELIMINATION KINETICS
Drugs can follow 2 types of ELIMINATION KINETICS
 FIRST ORDER (EXPONENTIAL) kinetics or
 ZERO ORDER (LINEAR) kinetics
FIRST ORDER (Exponential) Elimination Kinetics:
 “FIXED FRACTION” of dose eliminated / Unit Time
 CAN HANDLE ANY DOSE because “elimination
process / mechanisms” are available in PLENTY
 Does not get exhausted / choked
 i.e. it is NOT SATURABLE
 DOSE, and the Css reached after that Dose, have
LINEAR RELATIONSHIP with each other
 MOST DRUGS follow First Order Elimination 31

32. TYPES OF ELIMINATION KINETICS
ZERO ORDER (Linear) Elimination kinetics:
 “FIXED AMOUNT” (not Fraction) of the dose is
eliminated / Unit Time
 CAN HANDLE ONLY LIMITED AMOUNT OF DOSE
as the elimination process/mechanisms are
available in LIMITED amounts
 So, elimination process is easily choked – called
SATURABLE
 NO LINEAR RELATIONSHIP between DOSE & the
ACHIEVED Css
 Higher doses yield DISPROPORTIONATELY HIGH
plasma concentration
 Only FEW DRUGS follow ‘Zero’ Order Elimination 32

33. 33

34. CALCULATING AVd OF A 1st ORDER DRUG correctly
 AVd = DOSE given  C0
(C0 = Plasma conc. at Zero hour after Drug inj.
i.e. instantly)
• EXPONENTIAL Curve
• 2 PHASES but not distinct
–Phase
 – Phase
PLASMACONC.(Arithm.scale)
012345
0 1 2 3 4 5 6
TIME (hr)
I.V. DOSE
 – PHASE (Fast) of
Distribution of drug
 – PHASE (Slow)
of Drug Elimination
34

35. CALCULATING AVd OF A 1ST ORDER KINETICS DRUG
 If Plasma Conc. is plotted in Log-Scale 
• Almost BI-LINEAR Curve
with 2 CLEAR SLOPES
•-Slope of Drug
Distribution (Fast)
•-Slope of Drug
Elimination (Slow)
– Phase
0 2 4 6 8 10 12
TIME (hr)
I.V. DOSE
PLASMACONC.(Log.scale)
1248163264
If DOSE = 300 mg, & C0= 30 mg/L
AVd = 30030 = 10 L
• Extrapolate -Slope
back to get C0 =30 mg/L
35
–Phase

36. CLINICAL IMPLICATIONS OF Vd
1. Vd TELLS US WHERE IN THE BODY, DRUG IS
LOCATED
2. Vd HELPS IN FINDING (the Starting) DOSE OF
A DRUG
3. Vd HELPS IN CORRECTING (Insufficient or
Excessive) DOSE OF A DRUG
4. Vd HELPS PREDICTING OF DISPLACEMENT
DRUG INTERACTIONS
5. Vd HELPS MAKE ADJUSTMENTS FOR
EXCESSIVE BODY WEIGHT VARIATIONS

37. A. Some drugs may be distributed
IN PLASMA ONLY
(Their Vd will be = approx 4 to 5 L)
28L
4L 10L
Plasma Interstitium
RBCs Intracellular
Space
CLINICAL IMPLICATIONS OF AVd
1. Vd TELLS US WHERE IN THE BODY, DRUG
IS LOCATED- ECF

38. B. Some drugs may be distributed in
EXTRA-CELLULAR FLUIDS ONLY
(Plasma + Interstitial fluid)
(Their Vd will be = approx 12-15 L)
28L
10L
Plasma Interstitium
RBCs Intracellular
Space
4L
CLINICAL IMPLICATIONS OF AVd
Vd TELLS WHERE DRUG IS LOCATED
ECF

39. C. Lipophilic Drugs Cross Cell
Membranes & Distribute
UNIFORMLY IN TOTAL BODY WATER
(Their Vd will be = APPROX. 40 L)
28L
4L 10L
Plasma Interstitium
RBCs Intracellular
Space
CLINICAL IMPLICATIONS OF AVd
Vd TELLS WHERE DRUG IS LOCATED-

40. D. Some drugs
• BIND STRONGLY TO TISSUES  So
 their Plasma Levels are VERY LOW
Gives VERY HIGH Vd VALUE
(>100 L  DIGOXIN, CHLOROQUINE
which is unreal  So APPARENT Vd)
28L
4L 10L
Plasma Interstitium
RBCs Intracellular
Space
CLINICAL IMPLICATIONS OF AVd
Vd TELLS WHERE DRUG IS LOCATED -

41. CLINICAL IMPLICATIONS OF AVd
TO SUM UP 
 IF Vd = 5 - 15 L  DRUG IS MAINLY IN THE
PLASMA / E.C.F.  Drugs will act on Surface
Receptors; No action on Intracellular Targets
 IF Vd  42 L DRUG IS IN TOTAL BODY H2O
(60% of Body Wt) Intracellular Action also
 VERY HIGH Vd e.g. 100 L  SEQUESTRATED
IN TISSUES LITTLE DRUG IN PLASMA
 SUCH DRUGS CAN NOT BE REMOVED
BY DIALYSIS IN CASE OF OVER-DOSE
TOXICITY e.g. CHLOROQUINE, DIGOXIN
• BUT THE DRUGS WITH LOW Vd CAN BE
EASILY REMOVED BY DIALYSIS 41

42. CLINICAL IMPLICATIONS OF AVd
2.Vd HELPS IN FINDING THE ‘Starting’
DOSE OF A DRUG -
42
Vd =
DOSE
Plasma Conc.
Or DOSE = Vd x Plasma Conc.
(Needed) (Desired)
 Desired (Therapeutic) Plasma Conc. Range
for COMMUNITY is known for most Drugs
 Fine Titration of dose can subsequently be
done for INDIVIDUAL patient

43. CLINICAL IMPLICATIONS OF AVd
3. Vd helps in “CORRECTING the DOSE”
(a) INSUFFICIENT Dose:
Let INSUFFICIENT Dose be = D1
& Plasma Conc. achieved by it = C1
then D1 = Vd x C1 (Already in body)
Let NEW Needed Dose be = D2
& New Desired Plasma Conc. be = C2
then D2 = Vd x C2 (Needed in body)
Therefore Increase in Dose = D2 – D1
So (D2 – D1) = (Vd x C2) – (Vd x C1)
= Vd (C2 – C1)
(b) EXCESS DOSE: (Showing ADRs)
‘Reverse Procedure’ should be followed 43

44. CLINICAL IMPLICATIONS OF AVd
4. Vd & DISPLACEMENT INTERACTIONS
 LARGE Vd value means 
Lot of Drug Distributes to Peripheral
Tissues / Intracellular Water 
Plasma Levels will remain LOW
 When Displacement Interaction occurs
 Lot of ‘Displaced Drug’ is again ‘mopped
up & trapped’ by Peripheral Tissues
 Minimal Change occurs in Plasma Conc.
 ?? Displacement Drug Interactions will
be INSIGNIFICANT
44

45. CLINICAL IMPLICATIONS OF AVd
4. Vd & DISPLACEMENT-INTERACTIONS
(contd)
 SMALL Vd value means Drug is mainly in
Plasma / E.C.F. (Central Compartment)
 When Displacement Interaction occurs
a Lot of Displaced Free Drug will remain
in Plasma /E.C.F.
 SIGNIFICANT RISE in plasma conc. seen
 Clinical ‘OVERDOSE CONSEQUENCES’
can occur Sp. With Narrow T.I. Drugs
45

46. CLINICAL IMPLICATIONS OF AVd
5. Vd & BODY Wt. CONSIDERATIONS
 Vd VALUES (Volume) are for 70 kg Wt
(L / 70 kg; or mL / kg body wt.)  
 CORRECTIONS WOULD BE REQUIRED FOR
OVER-WEIGHT PATIENTS –
EXTRA FAT - OBESE PATIENTS
WATER-LOADED - PATIENTS with
ASCITIS, EDEMA, PLEURAL EFFUSION
 DRUGS CAN BE
LIPOPHILIC (preferring Fatty tissues) or
HYDROPHILIC (distributing more in Water)
46

47. CLINICAL IMPLICATIONS OF AVd
Vd & BODY Wt. CONSIDERATIONS-contd
 OBESE Patient: For Hydrophilic Drugs
(Gentamicin, Digoxin) Vd should be
calculated from “IDEAL BODY WEIGHT”
(which ignores excess fat content)
 IDEAL BODY Wt =
Males: 52+1.9 kg/inch height above 5 ft.
Females: 49+1.7 kg/inch height above 5 ft. 47

48. CLINICAL IMPLICATIONS OF AVd
Vd & BODY Wt. CONSIDERATIONS- contd
 WATER LOADED Patient:
 MEASURE THE ACTUAL Wt. OF PATIENT
 Make a ‘Rough Estimate of Excess Fluid’
 SUBTRACT Wt. of “Estimated Excess H2O”
 NOW CALCULATE Vd from Patient’s
“CORRECTED” Wt.
 FINALLY, ADD TO THIS ESTIMATED Vd,
1L / Kg OF ESTIMATED EXCESS WATER
 IMPORTANT FOR DRUGS DISTRIBUTING
MAINLY IN WATER; e.g. GENTAMICIN
48

49. 49
3.
ELIMINATION OF DRUG
[ T ½ ]

50. 3. ELIMINATION OF DRUG
(HOW LOG DRUG STAYS IN BODY)
FIRST WE NEED TO RECALL THAT –
ELIMINATION KINETICS of drugs can be
of 2 Types
FIRST ORDER (EXPONENTIAL) or
ZERO ORDER (LINEAR)
50

51. ELIMINATION OF DRUG
(HOW LOG DRUG STAYS IN BODY)
1. FIRST ORDER (Exponential) Kinetics:
MOST DRUGS follow 1st Order Kinetics
 Of the dose present in the body
“A FIXED FRACTION” is Eliminated
per Unit Time
 Actual “amount” eliminated per unit
time decreases progressively as dose
remaining in body decreases
1st Order Kinetics CAN HANDLE
ALMOST ANY DOSE
Elimination Process NOT SATURABLE51

52. ELIMINATION OF DRUG
2. ZERO ORDER (Linear) Kinetics 
 Seen in case of FEW DRUGS ONLY
 Of the given dose a “FIXED AMOUNT is
Eliminated per Unit Time
 ELIMINATING ENZYMES –
are in Limited Availability
Can handle only Limited Amount of Dose
 Process is SATURABLE With Higher Dose
Plasma Level Rises Disproportionately.
52
WE WILL NOW DISCUSS MAINLY
FIRST ORDER KINETICS
(as most drugs follow it)

53. ELIMINATION OF DRUG
FIRST FEW TERMINOLOGIES:
ELIMINATION
CLEARANCE (CL)
ELIMINATION RATE
ELIMINATION RATE CONSTANT
(Kel, ke, k)
53

54. ELIMINATION OF DRUG
(How long drug stays in body?)
TERMINOLOGIES:
1. ELIMINATION:
 SUM-TOTAL of the Processes of
“METABOLISM + EXCRETION” of drug
 THESE PROCESSES HELP TO
“CLEAR” the PLASMA of its Drug Content
 DESCRIPTIVE TERM helped to evolve the
term  “CLEARANCE”
54

55. ELIMINATION OF DRUG – (How long drug stays in body?)
2. CLEARANCE (CL):
If Plasma Conc. = 2 µg/mL
& Drug Removed = 400 µg/min
 Vol. of Plasma totally “Cleared” of drug
=400÷2 = 200 mL/min  Clearance
CL is defined as the “VOLUME” of Plasma /
Blood which is (Theoretically) completely
cleared of its drug PER UNIT TIME
Expressed as L/hr/70 kg (or mL/min/70 kg)
Many organs may participate in clearance
So, unless specified, CL means CLTOTAL
i.e. Cleared by All Organs
CLTOTAL = CLHEPATIC + CLRENAL + etc. + etc…..55

56. ELIMINATION OF DRUG – (How long drug stays in body?)
3. ELIMINATION RATE (Rate of Elimination):
(HOW MUCH drug is eliminated/Unit Time?)
In the previous slide 
Clearance = 200 mL/min
Blood/Plasma Conc. = 2 µg/mL
Elimination Rate = 200x2 = 400 µg/min
 Elimination Rate = CL x C
(400 µg/min) (200 mL/min) (2 µg/mL)
 Expressed as Amount per Unit Time
e.g. µg / min or mg / hr
56

57. ELIMINATION OF DRUG – (How long drug stays in body?)
4. ELIMINATION RATE CONSTANT (Kel, ke, k):
(What “FRACTION” of Dose present in Body
is eliminated Per Unit Time?)
If Dose in Body = 2 g
& Drug Elimination Rate = 0.1 g / hr
 Fraction Eliminated = 0.1g / hr ÷ 2g
= 1/20th = 0.05/hr
So Kel / ke /k = 0.05 / hr
 Expressed as Fraction Per Unit Time
 Value of Kel / ke / k will always be <1
57

58. Kel can also be calculated from CL & Vd as follows-
 From previous slide 
Kel /ke /k = Elimination Rate ÷ Total Dose In Body
58
 Kel/ke/k CL ÷ Vd=
CL Kel=
Is Amount eliminated per
Unit Time. It is present
in Plasma Cleared / U
time i.e. “CL” (Volume)
is actually contained
in Total Body Water
 i.e. “Vd” (Volume)
÷
Can Rewrite
equation to
find “CL”
from Kel & Vd
x Vd

59. ELIMINATION OF DRUG
(How long drug stays in body?)
TO SUMMARIZE THE TERMINOLOGIES:
 ELIMINATION: Descriptive term; Includes
Two Processes  drug Metabolism &
Excretion
 CLEARANCE (CL): What Volume of plasma
is cleared of its drug content per Unit Time
 ELIMINATION RATE: What Amount from
the administered dose is eliminated per
Unit Time
 ELIMINATION RATE CONSTANT (Kel/ke/k):
What Fraction of administered dose is
eliminated per Unit Time 59

60. ELIMINATION OF DRUG
(How long drug stays in body?)
DRUG PATTERN in blood concentration
depends on the 
MODE OF DRUG ADMINISTRATION
1. I.V. A. SINGLE (Bolus) DOSE
B. CONTINUOUS (INFUSION)
C. INTERMITTENT (REPEATED)
2. ORAL: A. SINGLE DOSE
B. INTERMITTENT (REPEATED)
3. Other Routes
4. UNIFORM or NON-UNIFORM DOSING
A. Stepping up Dosing
B. Stepping down Dosing, or
C. LOADING & Maintenance Dosing 60

61. 1A. SINGLE I.V. DOSE (Bolus)
ELIMINATION OF 1ST ORDER DRUGS WHEN
SINGLE I.V. DOSE IS GIVEN (as Bolus)
61

62. 1A. SINGLE I.V. DOSE (Bolus)
UNDERSTANDING DRUG’S
BEHAVIOR IN BLOOD & BODY?
How Long the Dose Stays in the Body
(or In How Much Time is the Dose
“Nearly Totally Eliminated”)
ELIMINATION OF 1ST ORDER DRUGS WHEN
SINGLE I.V. DOSE IS GIVEN (as Bolus)
62

63. 1A. SINGLE I.V. DOSE – GRAPHIC CALCULATION OF TIME
NEEDED FOR “NEAR TOTAL” ELIMINATION OF A DOSE?
Plasma Con. Falls to ½ its initial level:
from 3216 (50% Eliminated)
168 (50+25=75% Elimin)
84 (50+25+12.5% " " )
42 (50+25+12.5+6.25%
= 93.75% Elimin)
Each in 8 hr
Plasma Half
Life (T ½) of
Drug = 8 hr
CPLASMA fell 93.75% (32 to 2 µg/ml) in 4 x T ½ (32 hr)
I.V. DRUG
DISTRIBUTION
[α] PHASE
ELIMINATION
[β] PHASE
0 4 8 12 16 20 24 28 32 36
TIME (HOURS)
16
2
8
4
1
64
32
PlasmaLog-Concentration(µg/mL)
8 hr
8hr
8hr
8hr
63

64.  PLASMA HALF LIFE (T ½ ) OF DRUG:
Time needed for Plasma Concentration to
decline to HALF its Initial Value
(it means 50% of the Dose present in
body at that time has been eliminated)
 In 4xT½ 93.75% (~94%) Dose Eliminated
(only ~6% Dose remains in body)
 In 5xT½ 96.875% (~97%) Dose Eliminated
(only ~3% Dose remains in body)
 In 4-5 Half Lives “NEAR TOTAL” (94-97%)
Dose is Eliminated (Washed out) from
the Body  “WASH OUT TIME”
TIME NEEDED FOR ELIMINATION OF A DOSE
& PLASMA HALF LIFE (T ½)
64

65. “Whatever the Dose”  its 94–97% (i.e. Nearly
Total) is Eliminated from the Body in 4-5 x T ½
time in FIRST ORDER KINETICS drugs
i.e. T ½ is not related to Dose.
T ½ is INDEPENDENT of the DOSE
PARACETAMOL T ½ = 2 hr
(Near Total Elimination will need = 8-10 hr)
PROPRANOLOL T ½ = 3.9 hr
(Near Total Elimination will need = 15.6-19.5 hr)
DIGOXIN T ½ = 50 hr
(Near Total Elimination will need = 200-250 hr)
TIME for “NEAR TOTAL” ELIMINATION OF A DOSE
 Relation with Plasma T ½
65

66. Pharmacokinetics-Spot-1
Bioavailability (F) for the following
2 drugs is-
Propranolol 26%
Atenolol 56%
Q. What is the ONE MOST IMPORTANT Reason for
LOW Bioavailability of Propranolol?
(Answer in few words-Maximum one line)
Answer: First Pass Metabolism (or Pre-Systemic
Metabolism)

67. Pharmacokinetics-Spot-2
Vd (Volume of Distribution) for Digoxin is 500
Liters (per 70 kg.)
Q.1. Where in the body is most of the drug
present?
(Answer in max 4-5 words)
Q.2. Can Dialysis be useful in treating patient
with Digoxin overdose toxicity?
(Answer only as Yes or No)
Answer: Q.1. In Tissues;
Q.2. No

68. Pharmacokinetics-Spot-3
For Theophylline
Desired Plasma Concentration (C)
= 10 mg/L
Volume of Distribution (Vd)
= 35 L (per 70kg)
Q. Calculate the Dose (needed) of Theophylline.
Answer: Dose = Vd x C i.e. 35x10=350 mg

69. Pharmacokinetics-Spot-4
FOR ATENOLOL-
DESIRED PLASMA CONCENTRATION (C) = 1mg/L
VOLUME OF DISTRIBUTION (Vd) = 67L ( per 70kg)
Q. Calculate the Dose (needed) of Atenolol.
Answer: Dose = Vd x C i.e. 67x1=67 mg

70. Pharmacokinetics-Spot-5
Drug 'X' was given in 20 mg Bolus Dose.
Plasma concentration at Time Zero (C0) was
found to be 5 mg/L
Q. What is the Vd (Volume of Distribution) for Drug
'X‘?
Answer: Vd = Dose/C i.e. 20/5 = 4 Liters

71. Pharmacokinetics-Spot-6
Two Samples 'A' & 'B', of the same drug showed following
absorption data-
A B
‘F' (Bioavailability) 56% 57%
T-max (time to reach 20 min 48 min
peak conc.)
Q.1 Are the samples 'A' & 'B‘ Bioequivalent
or Bio-inequivalent?
Q.2 Why/ Why not (few words-maximum one line)?
Answer: Q.1- Bio-inequivalent
Q.2- Differing Tmax, though AUC nearly
same.

72. Pharmacokinetics-Spot-7
For Paracetamol-
CL (Clearance) = 20 L/ hr
'C' (Plasma concentration) = 15 mg/L
Q. Calculate "Elimination Rate" of Paracetamol.
Answer:
Elim Rate = CLxC
= 20x15
= 300 mg/hr

73. Pharmacokinetics-Spot-8
For Drug 'X'-
Total Dose Given =1000 mg
Elimination Rate = 200 mg/hr
Q. Calculate the Elimination Rate Constant (Kel/
Ke/ K) of the Drug 'X'.
Answer:
Kel (or K) = Elim Rate/ Total Dose in body
= 200/1000
= 0.2/hr

74. Pharmacokinetics-Spot-9
Ciprofloxacin (T ½ = 4.1hr) is to be given for few
days to a patient.
Q. How much time will be needed for Ciprofloxacin
to reach the Steady State Concentration (Css)?
Answer:
4-5 T ½ needed;
i.e. 4.1x 4 or 5
= 16.4 to 20.5 hr

75. THANKS
75