title: Lack of multiple dosing effect of sertindole on the pharmacokinetics of alprazolam in healthy volunteers.
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 t1/2 value (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 x 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.
authors.affiliation: Department of Pharmacokinetics and Biopharmaceutics, Abbott Laboratories, Abbott Park, IL 60064-3500, USA. shekman.wong@abbott.com
authors.forename: S L
authors.initials: SL
authors.lastname: Wong
authors.forename: C
authors.initials: C
authors.lastname: Locke
authors.forename: J
authors.initials: J
authors.lastname: Staser
authors.forename: G R
authors.initials: GR
authors.lastname: Granneman
mesh_terms: D000328:Adult; D000525:Alprazolam / Q000493:pharmacokinetics*; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D005838:Genotype; D006207:Half-Life; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male
chemical_list: D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; D019389:Cytochrome P-450 CYP2D6; C066304:sertindole; D000525:Alprazolam