Prescriptions Into Practice: Bupropion

Pharmacokinetics Bupropion is a racemic mixture. The pharmacologic activity and pharmacokinetics of the individual enantiomers have not been studied. Bupropion follows biphasic pharmacokinetics best described by a 2-compartment model. The terminal phase has a mean half-life of about 21 hours, while the distribution phase has a mean half-life of three to four hours. Absorption: Bupropion has not been administered intravenously to humans; therefore, the absolute bioavailability in humans has not been determined. Following oral administration of bupropion to healthy volunteers, peak plasma concentrations of bupropion are achieved within three hours. At steady state, the mean peak concentration (Cmax) following a 150mg dose every 12 hours is 136ng/ml. In a single-dose study, food increased the Cmax of bupropion by 11% and the extent of absorption as defined by area under the plasma concentration (AUC) by 17%. Distribution: Bupropion is 84% bound to plasma proteins at concentrations up to 200mcg/ml. The extent of protein binding of the hydoxybupropion metabolite is similar to that for bupropion, whereas the extent of protein binding of the threohydrobupropion metabolite is about half that seen with bupropion. The volume of distribution (Vss/F) estimated from a single 150mg dose given to 17 subjects is 1,950L (20% CV). Metabolism: Bupropion is metabolized by CYP 2B and CYP 3A4 systems into three active metabolites, hydroxybupropion, threohydrobupropion and erythohydrobupropion. The potency and toxicity of the metabolites relative to bupropion have not been fully characterized. However, it has been demonstrated in an antidepressant screening test in mice that hydroxybupropion is one half as potent as bupropion, while threohydrobupropion and erythohydrobupropion are 5-fold less potent than bupropion. Excretion: The mean apparent clearance (Cl/F) estimated from 2 single-dose (150mg) studies are 135 (+/-20%) and 209L/hr (+/-21%). Following chronic dosing of 150mg of bupropion every 12 hours for 14 days (n=34), the mean Cl/F at steady state was 160L/hr (+/-23%). The mean elimination half-life of bupropion estimated from a series of studies is approximately 21 hours. Estimates of half-lives of metablites determined from a multiple-dose study were 20 hours for hydroxybupropion, 37 hours for threohydrobupropion and 33 hours for erythrobupropion. Following oral administration of 200mg of 14C-bupropion in humans, 87% and 10% of a radioactive dose was recovered in the urine and feces, respectively. The fraction of the oral dose of bupropion excreted unchanged was only 0.5%.