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Effects of verapamil and diltiazem on the pharmacokinetics and pharmacodynamics of buspirone

, : Effects of verapamil and diltiazem on the pharmacokinetics and pharmacodynamics of buspirone. Clinical Pharmacology and Therapeutics 63(6): 640-645

Background. Buspirone has an extensive first-pass metabolism, which makes it potentially susceptible to drug interactions. The aim of this study was to investigate possible interactions of buspirone with verapamil and diltiazem. Methods. In a randomized, placebo-controlled, three-phase crossover study, nine healthy volunteers received either 80 mg verapamil, 60 mg diltiazem, or placebo orally three times a day. On day 2, after the fifth dose, 10 mg buspirone was given orally. Plasma concentrations of buspirone, verapamil, and diltiazem were determined up to 18 hours, and the effects of buspirone were measured up to 8 hours. Results. Verapamil and diltiazem increased the area under the buspirone plasma concentration-time curve (AUC (0-infin)) 3.4-fold (p < 0.001) and 5.5-fold (p < 0.001), respectively. The peak plasma concentration of buspirone was increased 3.4-fold (p < 0.001) and 4.1-fold (p < 0.001) by verapamil and diltiazem, respectively. The effect of diltiazem on the AUC(0-infin) of buspirone was significantly (p < 0.05) greater than that of verapamil. The elimination half-life of buspirone was not changed by verapamil and diltiazem. Of the six pharmacodynamic variables, only the subjective overall drug effect of buspirone was significantly increased with verapamil (p < 0.05) and diltiazem (p < 0.05). Side effects of buspirone occurred more often (p < 0.05) with diltiazem than with placebo. Conclusions. Both verapamil and diltiazem considerably increase plasma buspirone concentrations, probably by inhibiting its CYP3A4-mediated first-pass metabolism. Thus enhanced effects and side effects of buspirone are possible when it is used with verapamil, diltiazem, or other inhibitors of CYP3A4.


PMID: 9663178

DOI: 10.1016/S0009-9236(98)90087-X

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