Clinical Pharmacokinetics of Fluvoxamine: Applications to Dosage Regimen Design

Background: The disposition characteristics and pharmacokinetic parameters of drugs providefundamental data for designing safe and effective dosage regimens. A drug’s volume of distribution,clearance, and the derived parameter, half-life, are particularly important, as they determine the degreeof fluctuation between a maximum and minimum plasma concentration during a dosage interval,the magnitude of the steady-state concentration, and the time to reach a steady-state plasma concentrationupon chronic dosing. Potential drug-drug interactions can be predicted with knowledge of affinitiesfor various cytochrome P450 (CYP) isozymes. Method: The literature was searched for informationrelated to the pharmacokinetic properties of fluvoxamine and reports of its involvement indrug interactions. Results: The primary pharmacokinetic variables for fluvoxamine have been estimatedin single and multiple dose studies in animals, healthy volunteers, and patients. Fluvoxamine iswell absorbed after oral administration, widely distributed in the body, and eliminated with a meanhalf-life of 15 hours and a range from 9 hours to 28 hours. Its disposition is altered in hepatic, but notrenal, disease. Data from elderly subjects reflect a modest need for dosage adjustment in this population.Fluvoxamine produces no active metabolites. The specific cytochrome isozymes involved in thehepatic elimination of the drug are undefined. Data from studies relating the plasma concentration offluvoxamine to its clinical effects do not support routine plasma concentration monitoring in depressionor anxiety disorders. Fluvoxamine has prominent affinity for the CYP1A2 isozyme, lesser affinityfor the CYP3A4 and CYP2C isozymes, and minimal affinity for CYP2D6. This profile suggeststhe need for careful dosage adjustment when used together with some drugs that have a narrowtherapeutic range in order to minimize inhibiting their metabolism. Conclusion: Overall, the pharmacokineticprofile of fluvoxamine is adequately defined to provide guidelines for developing safe andeffective dosage regimens for most types of patients.