COMPETENCIES FOR PHARMACOKINETICS AND BIOPHARMACEUTICS (46:138)

These competencies have been developed to guide students in assessing their acquisition of course material taught by Dr. Svensson in the Pharmacokinetics and Biopharmaceutics course (46:138) of the P-2 year in the Doctor of Pharmacy program at The University of Iowa. Exams #1 and #3 will be developed such that at least 75% of the exam material will be based on the competencies listed below. Competencies are listed for each lecture topic (some topics cover more than one class period). It is important to recognize that the material builds as the course progresses. Thus, completion of a later competency may necessitate mastery of a competency for an earlier topic.

Upon successful mastery of the material presented in class, together with the reading and homework assignments, students should be able to:

Determinants of Pharmacologic Effect

1. Describe the primary means used to characterize pharmacologic effect.

2. Define and differentiate the terms pharmacokinetics and pharmacodynamics.

3. Identify the potential sources of variability in disposition of a xenobiotic after various routes of administration.

4. Describe the importance of variation in the concentration-effect relationship in determining the pharmacologic effect that is observed.

Passage of Xenobiotics Across Biological Membranes

1. Differentiate between passive diffusion, facilitated diffusion, and active transport.

2. Identify how various physicochemical characteristics of xenobiotics influence their biotransport.

3. Identify and describe the primary mechanisms of intestinal drug absorption.

4. Characterize the impact of efflux proteins at various anatomical sites (i.e., intestinal, placental, and blood-brain barrier) on the concentration and pharmacologic effect achieved.

Effect of Route of Administration on Drug Disposition and Action

1. Compare and contrast the effects of various routes of xenobiotic administration on the onset, intensity, and duration of pharmacologic effect.

2. Compare and contrast the advantages and disadvantages of various routes of xenobiotic administration.

3. Describe the significance and impact of the first-pass effect after oral administration.

4. Describe how formulation characteristics influence the disposition and action of drugs after various routes of administration (especially via the pulmonary and ophthalmic routes).

Distribution of Xenobiotics

1. Identify the 4 factors that determine the extent of xenobiotic distribution in the body.

2. Define the terms distribution and apparent volume of distribution.

3. Identify 4 mechanisms by which xenobiotics may gain access to the central nervous system.

4. Based on knowledge of the molecular weight and polarity, identify the likelihood that a xenobiotic will significantly accumulate in fetal blood/tissue.

Routes of Elimination of Xenobiotics

1. Identify 4 factors that influence the degree by which a xenobiotic is eliminated via the renal route.

2. Determine the impact of enterohepatic recirculation on the elimination of xenobiotics.

3. Identify the primary contributors to variability in drug concentration and, as a consequence, pharmacologic effect.

4. Describe the relationship between molecular weight and the fraction of a drug eliminated via biliary excretion.

Pharmacogenetics

1. Define the term pharmacogenetics.

2. Differentiate between genotype and phenotype.

3. Identify the major xenobiotic metabolizing enzymes that display genetic polymorphism.

4. Describe mechanisms by which allelic variation in xenobiotic metabolizing enzymes may result in altered metabolism of xenobiotics.

5. Determine the pharmacologic consequences of a genetic polymorphism in the enzyme responsible for metabolizing a drugs (i.e., will pharmacologic effect increase, decrease, or remain unchanged?).

Noncompartmental Pharmacokinetics

1. Define the terms clearance, extraction ratio, systemic clearance, mean residence time, mean transit time, mean absorption time.

2. Given drug concentration versus time data, calculate the AUC and AUMC for a drug.

3. Given the AUC and AUMC for a drug, determine the clearance, volume of distribution at steady-state, and the mean residence time.

4. Calculate and compare the mean absorption time for a two drug products made by different manufacturers.

Hepatic Clearance

1. Identify the three independent determinants of hepatic clearance.

2. Given hepatic clearance and hepatic blood flow data, determine whether a drug is perfusion-rate limited or exhibits restrictive hepatic clearance.

3. Describe and contrast the effect of changes in enzyme activity or hepatic blood flow on the blood concentration versus time curve and key pharmacokinetic parameters after oral and intravenous administration for low and high intrinsic clearance drugs.

4. Describe and contrast the effect of changes in plasma protein binding on the steady-state free and total concentrations of both low and high hepatic clearance drugs.

5. Provided data on total clearance, hepatic blood flow, and urinary excretion, determine the contribution of the liver to overall drug elimination.

Metabolite Kinetics

1. Compare and contrast the pharmacokinetic and pharmacologic consequences of formation rate-limited and elimination rate-limited metabolite disposition.

2. Describe the pharmacokinetic and pharmacologic impact of metabolic interconversion.

Pharmacokinetic Drug Interactions

1. Identify the potential sources for drug-drug interactions from a mechanistic perspective.

2. Identify the most clinically significant source of drug-drug and drug-nutrient interactions.

3. Given the pharmacokinetic parameters of a drug before and after the administration of a second drug, determine a) if there is evidence for a pharmacokinetic drug interaction and b) the mechanism of such interaction.

4. Provided key pharmacokinetic characteristics of a drug, predict the likelihood of a clinically significant drug interaction upon the addition of a second drug.

Dose- and Time-Dependent Pharmacokinetics

1. Compare and contrast the relationship between dose and key pharmacokinetic parameters (CL, t_1/2, C_ss, AUC) for drugs that display first-order or capacity-limited elimination.

2. Provided the pharmacokinetics parameters for a drug after several different doses, determine if the drug exhibits dose-dependent pharmacokinetics.

3. Identify pharmacokinetic process that may exhibit dose- and/or time-dependent pharmacokinetics.

Stereochemistry considerations

1. Identify which pharmacokinetic processes may exhibit stereoselectivity.

2. Describe the consequences of using a non-stereoselective assay to relate the concentration of a racemic mixture to the pharmacologic effect of a drug.

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