Drug Interactions with Antiretroviral Medications - Core Concepts

Pharmacokinetic and pharmacodynamics principles are fundamental to achieving the optimal response to antiretroviral drug therapy: successful antiretroviral therapy depends on attaining a therapeutic drug concentration that maximizes efficacy and minimizes toxicity.[1] Understanding drug interactions plays an important role for clinicians in providing effective and safe antiretroviral therapy. Drug interactions can be classified into one of two general categories: those that alter pharmacokinetics or those that alter pharmacodynamics. Pharmacokinetics involves the absorption, distribution, metabolism, and excretion of drugs in the body (Table 1), which is often influenced by a variety of biological, physiological, and chemical factors within each patient.[1] Pharmacokinetic studies are used to define the steady-state concentration of a particular drug, taking into account dose, bioavailability, and clearance, as well as drug interactions that can alter the systemic concentration of coadministered medications.[1] Pharmacodynamics describes the relationship of a drug and its effect on the body’s receptors, which can be affected by the number and affinity of receptors, drug concentration and genetics. In addition, genetic polymorphisms can influence the expression and availability of both receptor number and receptor affinity for a particular drug. Simplified, pharmacokinetics is what the body does to medication, and pharmacodynamics is what the medication does to the body. Pharmacokinetic interactions generally have greater clinical relevance. This Topic Review will primarily focus on pharmacokinetic interactions that involve antiretroviral medications.