- The document discusses pharmacokinetic models, specifically two-compartment models, to represent drug distribution and elimination in the body.
- A two-compartment model accounts for an initial distribution phase where the drug moves from the central to peripheral compartment, followed by an elimination phase where the drug declines in both compartments.
- Several parameters can be derived from a two-compartment model like rate constants, elimination half-life, apparent volumes of distribution, which provide insight into a drug's behavior in the body.
This presentation will give the students a basic knowledge about the pharmacokinetics of durgs. It will help them clear the basics before digging deep into the topic.
Methods For Assesment Of Bioavailability Anindya Jana
Bioavailability means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
Bioavailability studies are important in the Primary stages of development of a suitable dosage form for a new drug entity, determination of influence of excipients, patient related factors & possible interaction with other drugs on the efficiency of absorption, development of new formulations of the existing drugs, control of quality of a drug product during the early stages of marketing in order to determine the influence of processing factors, storage & stability on drug absorption
Plasma Drug Concentration Time Profile
Pharmacokinetic Parameter
Pharmacodynamic Parameter
Zero, First Order & Mixed Order Kinetic
Rates & Order Of Kinetics
Pharmacokinetic Models
Application Of Pharmacokinetic
It includes Introductory part about what is Dissolution...then Mechanism of Dissolution is elaborated...Theories of Dissolution also given..It also includes Factors affecting Dissolution profile..Along with References given below for easily searching..
This presentation will give the students a basic knowledge about the pharmacokinetics of durgs. It will help them clear the basics before digging deep into the topic.
Methods For Assesment Of Bioavailability Anindya Jana
Bioavailability means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
Bioavailability studies are important in the Primary stages of development of a suitable dosage form for a new drug entity, determination of influence of excipients, patient related factors & possible interaction with other drugs on the efficiency of absorption, development of new formulations of the existing drugs, control of quality of a drug product during the early stages of marketing in order to determine the influence of processing factors, storage & stability on drug absorption
Plasma Drug Concentration Time Profile
Pharmacokinetic Parameter
Pharmacodynamic Parameter
Zero, First Order & Mixed Order Kinetic
Rates & Order Of Kinetics
Pharmacokinetic Models
Application Of Pharmacokinetic
It includes Introductory part about what is Dissolution...then Mechanism of Dissolution is elaborated...Theories of Dissolution also given..It also includes Factors affecting Dissolution profile..Along with References given below for easily searching..
This PPT includes what role does Dosage form impart on absorption. Why it is important in absorption. what should be its nature and type of dosage form.
This presentation is about the process by which prolonged therapeutic activity of drug is achieved and it's importance. By this presentation you will learn about dosage regimen, steady state concentration, principle of superposition, drug accumulation, repetitive intravenous injections etc. By this you will also learn how to adjust the dose to the patient.
PHARMACOKINETIC MODELS
Drug movement within the body is a complex process. The major objective is therefore to develop a generalized and simple approach to describe, analyse and interpret the data obtained during in vivo drug disposition studies.
The two major approaches in the quantitative study of various kinetic processes of drug disposition in the body are
Model approach, and
Model-independent approach (also called as non-compartmental analysis).
DISSOLUTION
Dissolution is defined as a process in which a solid substance solubilises in a given solvent.
(i.e. mass transfer from the solid surface to the liquid phase.)
Three Theories:
Diffusion layer model / Film theory
Danckwert’s model / Penetration or Surface renewal theory
Interfacial barrier model / Double barrier or Limited solvation theory
This PPT includes what role does Dosage form impart on absorption. Why it is important in absorption. what should be its nature and type of dosage form.
This presentation is about the process by which prolonged therapeutic activity of drug is achieved and it's importance. By this presentation you will learn about dosage regimen, steady state concentration, principle of superposition, drug accumulation, repetitive intravenous injections etc. By this you will also learn how to adjust the dose to the patient.
PHARMACOKINETIC MODELS
Drug movement within the body is a complex process. The major objective is therefore to develop a generalized and simple approach to describe, analyse and interpret the data obtained during in vivo drug disposition studies.
The two major approaches in the quantitative study of various kinetic processes of drug disposition in the body are
Model approach, and
Model-independent approach (also called as non-compartmental analysis).
DISSOLUTION
Dissolution is defined as a process in which a solid substance solubilises in a given solvent.
(i.e. mass transfer from the solid surface to the liquid phase.)
Three Theories:
Diffusion layer model / Film theory
Danckwert’s model / Penetration or Surface renewal theory
Interfacial barrier model / Double barrier or Limited solvation theory
Pharmacokinetics (PK) is the study of how the body interacts with administered substances for the entire duration of exposure (medications for the sake of this article). This is closely related to but distinctly different from pharmacodynamics, which examines the drug's effect on the body more closely.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
1. Week 4 - Biopharmaceutics and
Pharmacokinetics
Pn. Khadijah Hanim bt Abdul Rahman
School of Bioprocess Engineering
University Malaysia Perlis
2. Multicompartment models:
intravenous bolus administration
• Pharmacokinetic models- represent drug
distribution and elimination in the body.
• A model should mimic closely the physiologic
processes in the body
• In compartmental models, drug tissue
concentration is assumed to be uniform within a
given hypothetical compartment.
• All muscle mass and connective tissues may be
lumped into one hypothetical tissue
compartment that equilibrates with drug from
the central (or plasma) compartment.
3. • Since no data is collected on the tissue mass,
the theoretical tissue concentration is
unconstrained and cannot be used to forecast
actual tissue drug levels.
• However, tissue drug uptake and tissue drug
binding from the plasma fluid is kinetically
simulated by considering the presence of a
tissue compartment.
4. • Multicompartment models were developed to
explain and predict plasma and tissue
concentrations for the behavior of these
drugs.
• In contrast, a one-compartment model is used
when the drug appears to distribute into
tissues instantaneously and uniformly.
5. • Central compartment
– These highly perfused tissues and blood make up
the central compartment.
• Multicompartment drugs
– multicompartment drugs are delivered
concurrently to one or more peripheral
compartments composed of groups of tissues
with lower blood perfusion and different affinity
for the drug.
6. Two Compartment Open Model
• Many drugs given in a single intravenous bolus
dose demonstrate a plasma level–time curve
that does not decline as a single exponential
(first-order) process.
• The plasma level–time curve for a drug that
follows a two-compartment model shows that
the plasma drug concentration declines
biexponentially as the sum of two first-order
processes—distribution and elimination.
7. • A drug that follows the pharmacokinetics of a
two-compartment model does not equilibrate
rapidly throughout the body, as is assumed for
a one-compartment model.
• In this model, the drug distributes into two
compartments, the central compartment and
the tissue, or peripheral compartment.
8. • Central compartment:
– represents the blood, extracellular fluid, and highly
perfused tissues. The drug distributes rapidly and
uniformly in the central compartment.
• Second compartment,
– known as the tissue or peripheral compartment,
contains tissues in which the drug equilibrates more
slowly.
• Drug transfer between the two compartments is
assumed to take place by first-order processes.
10. Distribution phase- represents the
initial, more rapid decline of drug from
the central compartment into tissue
compartment (line a)
• distribution phase- drug elimination
and distribution occur concurrently
•Net transfer of drug from central to
tissue compartment
•Fraction of drug in the tissue
compartment during distribution
phase increases to max.
•At max. tissue conc. – rate of drug
entry into tissue = rate of drug exit
from tissue.
•Drug in tissue compartment-equilibrium
with drug in central
compartment (distribution
equilibrium)
•Drug conc in both compartment
decline in parallel and more slowly
compared to distribution phase
The decline is 1st order process and
called elimination phase or β phase
(line b)
12. • compartment 1 is the central compartment
and compartment 2 is the tissue compartment.
• The rate constants k12 and k21 represent the
first-order rate transfer constants for the
movement of drug from compartment 1 to
compartment 2 (k12) and from compartment 2
to compartment 1 (k21).
13. Relationship between drug
concentrations in tissue and plasma
• The maximum tissue
drug concentration may
be greater or less than
the plasma drug
concentration.
14. • the rate of drug change in and out of the tissues:
15. • The relationship between the amount of drug in each
compartment and the concentration of drug in that
compartment is shown by:
where
– DP = amount of drug in the central compartment,
– Dt = amount of drug in the tissue compartment,
– VP = volume of drug in the central compartment, and
– Vt = volume of drug in the tissue compartment.
18. • The rate constants for the transfer of drug between
compartments are referred to as microconstants or
transfer constants, and relate the amount of drug
being transferred per unit time from one
compartment to the other.
• The constants a and b are hybrid first-order rate
constants for the distribution phase and elimination
phase, respectively.
19. • Equation
• Constants a and b- rate constant for distribution phase
and elimination phase
• Can be write as
• The constants A and B are intercepts on the y axis for
each exponential segment of the curve
21. Method of residuals
Method of residual- feathering or peeling,
useful for fitting a curve to the
experimental data of drug when drug does
not follow one compartment model.
E.g: 100 mg of drug administered by rapid
IV injection to a 70-kg healthy adult male.
Blood sample were taken periodically and
the following data were obtained:
22. When data is plotted, a curved
line is observed. The curved-line
relationship between logarithm
of the plasma conc and time
indicates that drug is distributed
in more than one compartment.
From these data, biexponential
equation, may be derived
The rate constant and intercepts
were calculated by method of
residuals
As shown in biexponential curve,
the decline in initial distribution
phase is more rapid than
elimination phase.
Rapid distribution phase
confirmed with constant a being
larger than constant b.
at some later time Ae-at will
approach 0, while Be-bt still have
value.
23. • Therefore,
• In common logarithms,
• From equation above, rate constant can be
obtained from the slope (-b/2.3) of a straight
line representing the terminal exponential
phase.
24. • The t1/2 for elimination phase (beta half life)
can be derived from the following
relationship:
• From Eg. b was found to be 0.21 hr-1. from this
info the regression line for terminal
exponential or b phase is extrapolated to the y
axis; y intercept = B or 15um/mL.
25. •Values from the extrapolated line are then substracted from the original
expremental data points and a straight line is obtained. This line represents
the rapidly distributed a phase
•The new line obtained by graphing the logarithm of residual plasma conc
(Cp- C’p) against time represents the a phase. The value for a is 1.8 hr-1 and
y intercept is 45ug/mL. elimination half life, t1/2 computed from b, has the
value of 3.3 hr.
26. • A no of pharmacokinetic parameters may be
derived by proper substitution of rate
constants a and b and y intercepts A and B to
following equations:
27. Apparent Volumes of distribution
• VD- parameter that relates plasma conc (Cp) to
the amount of drug in the body (DB)
• Drugs with large extravascular distribution/
high peripheral tissue binding- the VD is
generally large
• Polar drugs with low lipid solubility- VD is small
28. Volume of the Central compartment
• Useful to determine drug conc. after IV
injection
• Also refered as Vi = initial VD as the drug
distributes within plasma and other body
fluids
• Vi- generally smaller than terminal VD after
drug distribution to tissue is completed
• Vol of central compartment- generally greater
than 3L
29. • For polar drugs, initial Vol of 7-10 L- interpreted
as rapid drug distribution wthin plasma and
extracellular fluids
• E.g: Vp of hydromorphone about 24 L- possibly
becoz of rapid exit from plasma into tissues even
during initial phase.
• As in the case of one-compartment model- Vp
determined from the dose and instantaneous Cp.
• Vp useful in determination of drug clearance if k is
known
30. • In two-compartment model, Vp considered as
mass balance factor governed by mass
balance between dose (D) and Cp
• Ie. Drug conc x vol of fluid = dose at t=0
at t=0, no drug eliminated, Do= VpCp
• At t=0, all of drug in the body is in central
compartment
31. • Cp0 can be shown to be equal to A and B by
following equation:
• At t=0, e0=1, therefore
• Vp is determined from this equation by
measuring A and B after feathering the curve
32. • Alternatively, the vol of central compartment
may be calculated from the similar to
calculation of VD for one compartment model
• for two-compartment model
=
33. Apparent volume of distribution at
steady state
• At steady-state- the rate of drug entry into
tissue compartment from central
compartment = rate of drug exit from tissue
compartment into the central compartment
• Amount of drug in central compartment, Dp =
VpCp,
34. • Total amount of drug at steady state = Dt + Dp
• The apparent vol of drug at steady state (VD)ss
• Substitute of Dt and expresses Dp as VpCp
• (VD)ss- function of transfer constants, k12 and k21=
rate constants of drug going into and out of tissue
compartment
35. Extrapolated volume of distribution
• Where B= y intercept obtained by
extrapolation of the b phase of plasma level
curve to y axis. Can be calculated by this
equation:
36. Volume of distribution by area
• (VD)area = (VD)β – obtained through
calculations similar to those used to find Vp
except that rate constant b instead of
elimination rate constant, k.
• (VD)β calculated from total body clearance
divided by b (influenced by drug elimination in
the beta, or b phase).
37. • Total body clearance = , (VD)B may be
expressed as
• By substitution of kVp :
38. Drug in the tissue compartment
• Vt= apparent volume of the tissue compartment may
be calculated from knowledge of the transfer rate
constants and Vp:
• Calculation of amount of drug in tissue compartment
does not involve the use of Vt
• Vt
-provides an estimate for drug accumulation in the
tissues
-Vital in estimating chronic toxicity and duration of
pharmacologic activity to dose
39. • To calculate the amount of drug in tissue
compartment, Dt
40. Drug Clearance
• Clearance- vol of plasma that is cleared of
drug per unit time
• Clearance may be calculated without
consideration of compartment model
• Cl in the two-compartment model is the
product of (VD)β and b
41. Elimination rate constant
• In two-compartment, the elimination rate constant, k
represents the elimination of drug from the central
compartment
• b represents drug elimination during the beta or
elimination phase when distribution is mostly complete
• Plasma-drug level curve declines more slowly in b phase-redistribution
of drug out of tissue compartment
• b is smaller than k
• k- true elimination rate constant
• b- hybrid elimination rate constant- influenced by rate
transfer of drug in and out of tissue compartment
42. Three compartment open model
• Three compartment- two compartment model +
deep tissue compartment
• Central compartment- distributed most rapidly-highly
perfused tissues
• Compartment 2- less rapidly
• Compartment 3- very slowly- poorly perfused
tissues, i.e. bone/ fat
43. • Rates of flow of drug into and out of the
central compartment:
• A, B and C – y intercept of extrapolated lines
for central, tissue and deep tissue
compartment
• a, b and c – 1st order rate constant