Pharmacokinetics and Pharmacodynamics for Medical Students: A Proposed Course Outline

The discipline of pharmacokinetics (PK) applies mathematical models to describe and predict the time course of drug concentrations and drug amounts in body fluids.1–3 Pharmacodynamics (PD) applies similar models to understand the time course of drug actions on the body. Clinicians aremost concerned with pharmacodynamics—they want to know how drug dosage, route of administration, and frequency of administration can be chosen to maximize the probability of therapeutic success while minimizing the likelihood of unwanted drug effects. However the path to pharmacodynamics comes via pharmacokinetics. Because drug effects are related to drug concentrations, understanding and predicting the time course of concentrations can be used to help optimize therapy. The link of drug dosage to drug effect involves a sequence of events (Figure 1). Even when a drug is administered directly into the vascular system, the drug diffuses to both its pharmacologic target receptor and to other peripheral distribution sites where it does not have the desired activity but may exert toxic effects. Simultaneously, the drug undergoes clearance by metabolism and excretion. After oral administration, the situation is more complex, since the drug must undergo dissolution and absorption, then survive firstpass metabolism in the liver, before reaching the systemic circulation. Pharmacokinetics provides a rational mathematical framework for understanding these concurrent processes, and facilitates achieving optimal clinical pharmacodynamic effects more efficiently than trial and error alone. The following 3 clinical vignettes illustrate how familiarity with principles of pharmacokinetics and pharmacodynamics can facilitate optimal understanding and prediction of drug effects in human subjects and patients. Clinical Vignettes Case 1 A 30-year-old man has been extensively evaluated for recurrent supraventricular tachycardia (SVT), which is associated with palpitations and dizziness. No identifiable cardiac disease is evident, and other medical diseases have been excluded. The treating physician elects to start therapy with digitoxin, 0.1mg daily. Oneweek later the patient is seen again, and states that episodes of SVT are reduced in number. The plasma digitoxin level is 8 ng/mL (usual therapeutic range, 10–20 ng/mL). The dose is increased to 0.2 mg/day. At a follow-up visit 7 days later, the patient claims that symptoms attributable to SVT have disappeared completely. The plasma digitoxin level is 17.4 ng/mL. The patient continues on 0.2 mg/day of digitoxin. One month later the patient sees the physician on an urgent basis. He has diminished appetite and waves