The drug half-life (½) is the time it takes for the amount of drug in the body to be reduced by half. What factors influence the half-life of a drug? (Select all that apply)

Drug half-life is determined by how quickly the body eliminates a drug, which depends on two primary pharmacokinetic processes: metabolism and excretion. Metabolism, primarily hepatic, converts the drug into metabolites that are more easily removed. Excretion, primarily renal, eliminates the drug or its metabolites from the body. Together, these two processes define the rate at which plasma drug concentration falls by 50%, which is the definition of half-life. If either is impaired — for example, in liver or kidney disease — the half-life is prolonged, meaning the drug stays in the body longer and can accumulate to toxic levels. Drug toxicity is not a determinant of half-life; rather, toxicity can be a consequence of a prolonged half-life, not a cause of it. A loading dose is a pharmacokinetic strategy used to rapidly achieve a therapeutic concentration at the start of therapy; it affects the time to steady state but has no influence on the half-life of the drug itself. Half-life is an intrinsic pharmacokinetic property based on clearance and volume of distribution, not on the initial dose administered. Students commonly confuse cause and effect here — remember that toxicity results from altered half-life, it does not alter it.