ISSN:
1432-1041
Keywords:
Key words Buspiron
;
Fluvoxamine
;
Interaction
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Abstract Objective: The effects of fluvoxamine, a selective serotonin (5-HT) reuptake inhibitor antidepressant, on the pharmacokinetics and pharmacodynamics of buspirone, a non-benzodiazepine anxiolytic agent, were investigated. Methods: In a randomized, placebo-controlled, two-phase cross-over study, ten healthy volunteers took either 100 mg fluvoxamine or matched placebo orally once daily for 5 days. On day 6, 10 mg buspirone was taken orally. Plasma concentrations of buspirone and its active metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP), were measured up to 18 h and the pharmacodynamic effects of buspirone up to 8 h. Results: The total area under the plasma buspirone concentration-time curve was increased 2.4-fold (P 〈 0.05) and the peak plasma buspirone concentration 2.0-fold (P 〈 0.05) by fluvoxamine, compared with placebo. The half-life of buspirone was not affected. The ratio of the total area under the plasma concentration-time curve of 1-PP to that of buspirone was decreased from 7.4 [6.3 (SD)] to 4.4 (3.6) by fluvoxamine (P 〈 0.05). The results of the six pharmacodynamic tests remained unchanged. Conclusion: Fluvoxamine moderately increased plasma buspirone concentrations and decreased the production of the active 1-PP metabolite of buspirone. The mechanism of this interaction is probably inhibition of the CYP3A4-mediated first-pass metabolism of buspirone by fluvoxamine. However, this pharmacokinetic interaction was not associated with impairment of psychomotor performance and it is probably of limited clinical significance.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002280050548
