LACK OF CYP3A INHIBITION EFFECTS OF SERTINDOLE ON TERFENADINE IN HEALTHY-VOLUNTEERS

The effect of sertindole (a new selective antipsychotic compound) on t he pharmacokinetic disposition of terfenadine was investigated. Thirte en subjects who completed the study received a single 120 mg dose of t erfenadine alone or with concomitant 20 mg sertindole daily. The mean values for terfenadine C-max (alone: 2.42 +/- 1.48 ng/ml, in combinati on: 2.99 +/- 1.85 ng/ml) and AUC (29.6 +/- 18.9 vs 37.9 +/- 23.4 ngxhr /ml) did not change statistically significant in the presence of serti ndole (p > 0.05). Similarly, the mean C-max (531 +/- 195 vs 506 +/- 19 0 ng/ml) and AUC (3,728 +/- 1,163 vs 4,003 +/- 1,739 ngxhr/ml) values of carboxyterfenadine did not change statistically significant in the presence of sertindole (p > 0.05). The other pharmacokinetic parameter s of terfenadine and carboxyterfenadine such as T-max, t(1/2), as well as the carboxyterfenadine to terfenadine C-max and AUC ratios did not change in the presence of sertindole. Although terfenadine is a subst rate for CYP3A (cytochrome P-450 3A), while sertindole is a substrate for both CYP2D6 and CYP3A4, the results in this study suggest that ser tindole, at a clinical dose, is not an inhibitor of the metabolism of terfenadine.