Clinical Pharmacokinetics of Fluvoxamine: Applications to Dosage Regimen Design

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Background: The disposition characteristics and pharmacokinetic parameters of drugs provide fundamental 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 degree of 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 concentration upon chronic dosing. Potential drug-drug interactions can be predicted with knowledge of affinities for various cytochrome P450 (CYP) isozymes. Method: The literature was searched for information related to the pharmacokinetic properties of fluvoxamine and reports of its involvement in drug interactions. Results: The primary pharmacokinetic variables for fluvoxamine have been estimated in single and multiple dose studies in animals, healthy volunteers, and patients. Fluvoxamine is well absorbed after oral administration, widely distributed in the body, and eliminated with a mean half-life of 15 hours and a range from 9 hours to 28 hours. Its disposition is altered in hepatic, but not renal, 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 the hepatic elimination of the drug are undefined. Data from studies relating the plasma concentration of fluvoxamine to its clinical effects do not support routine plasma concentration monitoring in depression or anxiety disorders. Fluvoxamine has prominent affinity for the CYP1A2 isozyme, lesser affinity for the CYP3A4 and CYP2C isozymes, and minimal affinity for CYP2D6. This profile suggests the need for careful dosage adjustment when used together with some drugs that have a narrow therapeutic range in order to minimize inhibiting their metabolism. Conclusion: Overall, the pharmacokinetic profile of fluvoxamine is adequately defined to provide guidelines for developing safe and effective dosage regimens for most types of patients.

J Clin Psychiatry 1997;58(suppl 5):7–14