CLINICAL PHARMACOKINETICS OF FLUVOXAMINE

Fluvoxamine is a selective inhibitor of serotonin reuptake that is wid ely used in the management of depression. Following oral administratio n, the drug is absorbed efficiently from the gastrointestinal tract. P eak plasma concentrations are usually observed within 2 to 8 hours pos tdose for capsules and film-coated tablets and within 4 to 12 hours fo r enteric-coated tablets. Despite complete absorption, oral bioavailab ility may be incomplete probably because of first-pass metabolism. App roximately 77% of fluvoxamine is plasma protein bound. Only negligible amounts of fluvoxamine are excreted unchanged in urine. The drug is e xtensively biotransformed, mostly by oxidation, and at least 11 differ ent metabolites have been detected in human urine. None of the metabol ites is known to possess significant pharmacological activity. Followi ng administration of single doses, fluvoxamine shows a biphasic elimin ation with a mean terminal elimination half-life of about 15 to 20 hou rs. Steady-state plasma fluvoxamine concentrations are achieved 5 to 1 0 days after initiation of therapy and are 30 to 50% higher than those predicted from single-dose data. Preliminary data also suggest that p lasma drug concentrations may increase nonlinearly with increasing dai ly dosage. The relationship between plasma fluvoxamine concentration a nd clinical response has not been clearly defined. Fluvoxamine pharmac okinetics are substantially unaltered in the elderly, whereas higher p lasma drug concentrations (relative to dose) are observed in patients with alcoholic cirrhosis of the fiver. Fluvoxamine inhibits oxidative drug metabolising enzymes and, therefore, causes a number of clinicall y significant drug interactions. Drugs whose metabolic elimination is impaired by fluvoxamine include tricyclic antidepressants, alprazolam, bromazepam, diazepam, theophylline, phenazone (antipyrine), propranol ol, warfarin, methadone and carbamazepine.