Exam 1 learning objectives

Question 1

Describe the concepts of kinetic homogeneity and its significance for our use of the plasma drug concentration versus time curve data

Answer 1

1. Kinetic homogeneity: the predictable relationship between plasma drug concentration and the concentration at the site of action
2. we assume the plasma drug concentration directly relates to concentration in the tissues

Question 2

Define and differentiate between the terms biopharmaceutics, pharmacokinetics, clinical pharmacokinetics, and therapeutic drug monitoring

Answer 2

1. Biopharmaceutics: the interrelationship of the physicochemical properties of a drug, the dosage form in which the drug is given, and the route of administration on the rate and extent of systemic absorption
2. Pharmacokinetics: study of the time course of drug process that determine the concentration of drugs in body fluid and tissues over time (absorption, distribution, biotransformation, and excretion)
3. Clinical pharmacokinetics: the application of PK principles to the safe and effective therapeutic management of drugs in an individual pts
4. pharmacodynamics: the study of the detailed MOA by which drugs produce their pharmacologic effect. Refers to the relationship between drug conc. at the site of action and the resulting effect
5. Therapeutic drug monitoring: measurement of drug concentrations and assessment and application of the resulting concentrations to design safe and effective drug regimens

Question 3

Explain the functions of pharmacokinetic models; differentiate between compartmental and physiologic models

Answer 3

1. One-compartment model: all uniform distribution; all absorption is instantaneous and complete
2. Two-compartment model
3. Physiologic models
4. Non-compartmental

Question 4

Differentiate between zero-order and first-order elimination process characteristics and visual display on rectangular/linear versus semi-logarithmic graphing paper

Answer 4

1. Zero-order: The amount of drug eliminated does not change with the amount of drug/concentration in the body; the AMOUNT removed remains constant
2. First order: the amount of drug eliminated in a certain period of time is directly proportional to the amount of drug in the body; the FRACTION removed remains constant

Question 5

Explain the concepts of elimination rate constant, half-life, and area under the curve

Answer 5

1. Elimination rate constant: a fraction or percentage of the drug dose administered that is removed per unit of time
2. half-life: the time necessary for the drug concentration to decrease by 1/2 or 50%
3. AUC: determined by the dose administered and drug clearance

Question 6

Calculate the following PK parameters: Cp0/Cmax, Vd, Ke, t1/2, plasma drug conc. for a given time, time for a given plasma drug concentration, and AUC using an appropriate equation and units of measurement

Answer 6

Cp0: initial plasma drug concentration (same as Cmax)
Cmax: dose/Vd
Ke: (Ln Cp1/Cp2)/t
AUC: (C2+C1)/2)(T2-T1) + etc and terminal area

Question 7

Discuss the impact of changes to GI physiological factors that affect drug absorption and provide examples of these changes along with the resultant effect observed on drug absorption

Answer 7

1. Surface area: smaller decreased absorption
2. pH: affects the degree of ionization
3. Motility: sufficient residence time needed for absorption
4. Gastric emptying: Delayed gastric emptying slows the rate and impacts the extent of absorption
5. Perfusion: increases in the fed state, decreased perfusion will impact rate and possibly extent
6. Food: delays gastric emptying, alters pH, increases perfusion
7. disease

Question 8

Describe the term bioavailability as well as the concepts of gut wall metabolism, first-pass metabolism, and extraction ratio and predict the impact of each on oral drug bioavailability and the plasma drug concentration versus time curve

Answer 8

1. Bioavailability: fraction of the unchanged drug dose that is absorbed from the drug product and reaches the systemic circulation
2. Gut wall and first-pass metabolism: Biotransformation and metabolism occur within the intestine via CYP enzymes within the mucosal cells and/or liver
3. Pre-systemic metabolism: metabolism prior to reaching systemic circulation (decreased BA)
4. Extraction ratio: provides a direct measurement of drug removal from the liver following oral administration of a drug

Question 9

Compare and contrast the characteristics of the plasma drug concentration versus time curves following an oral vs IV bolus and immediate-release vs modified-release oral dosage form regarding absorption, Tmax, Cmax, elimination, AUC, and visual display