Antiepileptic drug interactions

This article reviews the potential interactions of antiepileptic drugs (AED s) and the pharmacokinetic and pharmacodynamic principles involved. It desc ribes the absorptive and distributive properties of AEDs and the effects on protein binding, hepatic metabolism, and elimination resulting from co-adm inistration of AEDs with food or other drugs. Drug behavior is a function o f absorption, metabolism, distribution, and elimination. Administration of either multiple AEDs or a combination of AEDs plus drugs for other conditio ns can modify any of these physiologic processes, possibly resulting in com plex interactions. These may include alterations in the bioavailability and absorption of a drug and changes in half-life and serum level through indu ction or inhibition of hepatic metabolism. In most cases, increases or decr eases in serum concentrations will signal a drug interaction. In other case s, clinically significant drug interactions remain undetected owing to appa rently stable serum concentrations. Go-administration of drugs may affect t he rate of clearance of one or both drugs. The effect on clearance varies, owing to genetic factors, patient characteristics (age and presence of co-m orbidities), and individual responses. AEDs that induce hepatic metabolism can also influence the metabolism of concomitantly administered non-epileps y medications and can interfere with oral contraceptives, as well as vitami ns D and K. Patients with renal insufficiency or advanced age may experienc e incomplete renal excretion and should receive reduced dosages of drug. Un derstanding the pharmacokinetics and pharmacodynamic properties of AEDs and the route of metabolism of all competing drugs is important for optimal ma nagement of patients with epilepsy and for prevention of avoidable drug int eractions.