Lack of multiple dosing effect of sertindole on the pharmacokinetics of alprazolam in healthy volunteers |
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Authors: | S. L. Wong C. Locke J. Staser G. R. Granneman |
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Affiliation: | (1) Department of Pharmacokinetics and Biopharmaceutics, D4PK, AP 13A, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-3500, USA Fax (+1) 847/938-5193, e-mail: shekman.wong@abbott.com, US;(2) Biostatistics Department, Abbott Laboratories, Abbott Park, Illinois, USA, US;(3) Psychopharmacology Venture, Abbott Laboratories, Abbott Park, Illinois, USA, US |
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Abstract: | The effect of sertindole (a new selective antipsychotic compound) on the pharmacokinetic disposition of alprazolam was investigated. Fourteen subjects who completed the study received a single 1 mg dose of alprazolam without or with concomitant sertindole 12 mg daily. Coadministration of sertindole and alprazolam led to a half-hour decrease (P < 0.05) in mean Tmax value (alone: 1.2 h, in combination: 0.7 h) and a 1.6-h increase in the mean t1/2value (12.5 ± 3.2 versus 14.3 ± 3.4 h, P < 0.05) of alprazolam. The mean Cmax (18.5 ± 4.9 versus 18.5 ± 4.8 ng/ml) and AUC (266 ± 68 versus 275 ± 57 ng⋅h/ml) values of alprazolam did not change statistically significantly in the presence of sertindole (P > 0.05). These pharmacokinetic changes are minor and not considered to be of clinical significance. Although both sertindole and alprazolam are substrate for CYP3A4 (cytochrome P-450 3A4), the results in this study suggest that sertindole is not an inhibitor of the metabolism of alprazolam. Received: 5 March 1997/Final version: 28 July 1997 |
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Keywords: | Sertindole Pharmacokinetics Alprazolam Schizophrenia Interactions |
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