Rene H Levy
Basic principles of pharmacokinetics and their application to the clinical setting, including: single-dose intravenous and oral kinetics, multiple dosing, nonlinear pharmacokinetics, metabolite kinetics, pharmacogenetics, and the role of disease in drug clearance and dose requirements, and kinetics of drug-drug interactions. Prerequisite: PCEUT 331. Offered: W.
The goals of this course are to provide the student with: (i) an understanding of the fundamental concepts of pharmacokinetics in humans; (ii) skills in applications of pharmacokinetics in therapeutic monitoring.
1. To define the basic pharmacokinetic parameters of a drug: volume of distribution, clearance terms, extraction ratio, elimination half life, unbound fraction and to understand how these parameters are related.
2. To differentiate between rate and rate constant.
3. To understand the role of compartment models in describing the time course of blood levels of drug in the body.
4. To differentiate between organ clearance, total body clearance, formation clearance of a given metabolite and the fraction of clearance associated with a given metabolic enzyme.
5. To describe the effect of protein binding on pharmacokinetic parameters (volume of distribution, clearance and half life) and on steady state plasma concentration.
6. To describe and define the pharmacokinetic parameters of a drug which can be determined using urinary excretion data.
7. To demonstrate how the first pass effect (upon oral administration) can be predicted.
8. To understand the time course of drug accumulation in the body during a constant rate infusion and the notion of steady state (or plateau) level.
9. To relate the time course of drug accumulation to the time course of drug elimination and to determine which pharmacokinetic parameters can be calculated.
10. To understand the concept of additivity of plasma levels upon intravenous or oral multiple dosing.
11. To understand the parameters governing the formation and elimination of metabolites.
12. To discuss the various sources of interpatient pharmacokinetic variability: metabolic isozymes, pharmacogenetics and drug interactions.
13. To understand the concept of Michaelis Menten pharmacokinetics and its consequences on the behavior of plasma levels; to define Michaelis Menten parameters.
14. To use relevant clinical pharmacokinetic data to demonstrate the ability to determine maintenance and loading doses of drugs in different patient populations.
15. To understand the effects of both intersubject and intrasubject variability in physiological and pathological parameters on using pharmacokinetic data to formulate individualized dosage regimens.
Student learning goals
General method of instruction
Class assignments and grading
1. To calculate pharmacokinetic parameters given sets of timed plasma concentrations after various routes of administration.
2. Given pharmacokinetic equations, to construct plots which demonstrate (i) the dependence of various pharmacokinetic parameters on dose of drug and (ii) the interdependence between parameters; (iii) the dependence of plasma concentration on changes in protein binding.
3. Given a table of pharmacokinetic parameters: (i) to calculate a dosing regimen; (ii) to predict extent of first pass effect (bioavailability).
4. Given a knowledge of enzymes involved in the metabolism of a drug, to predict the potential for pharmacogenetic differences in the population and the potential for metabolic drug interactions.
There will be three (3) midterm examination and one (1) final examination