Lack of multiple dosing effect of sertindole on the pharmacokinetics of alprazolam in healthy volunteers.
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.
Wong
S L
SL
Department of Pharmacokinetics and Biopharmaceutics, Abbott Laboratories, Abbott Park, IL 60064-3500, USA. shekman.wong@abbott.com
Locke
C
C
Staser
J
J
Granneman
G R
GR
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
D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; D019389:Cytochrome P-450 CYP2D6; C066304:sertindole; D000525:Alprazolam