RESUMO
BACKGROUND: Inter-ethnic differences exist in both pharmocodynamics and pharmocokinetics. CYP3A is the most abundant cytochrome P450 enzyme in human liver and is responsible for the metabolism of a large number of drugs and xenobiotics. AIM OF STUDY: The purpose of the present study was to determine whether there are differences in the metabolism and drug responsiveness to triazolam, a substrate of CYP3A, in American blacks and whites. METHODS: Eight American blacks and eight age - and body weight- matched whites receved orally a triazolam 0.375 mg tablet in a double-blind placebo-controlled randomized study. Plasma concentrations and effects of triazolam were measured at multiple time points over 24 hours. The pharmacodynamics of triazolam were examined by measurement of postural sway, digital symbol substitution testing (DSST), and a visual analog scale (VAS) of drowiness. Sensitivity, or the drug effect at a given concentration, was determined. RESULTS: Following oral administration of triazolam, the AUC was significantly lower in blacks (625 +- 160 ng/ml/min) (P<0.05). The systemic clearance of triazolam was three and a half fold higher in blacks (6.6 +- 2.0 vs 1.8 +- 0.2 ml/min/kg in whites, P<0.05) resulting in a shorter elimination t 1/2 (98 +- 24 vs 199 +- 29 min, P<0.05). Triazolam significantly increased postural sway and drowsiness and impaired DSST in both groups. However, there was no significant differences between the two groups in drug effects such that a similar effect of triazolam was observed in blacks with lower plasma concentration. When compared to whites, the sensitivity to triazolam was significantly higher in blacks (P<0.05). CONCLUSIONS: This study demonstrates increased clearance and increased sensitivity to triazlam in American blacks. These findings may have major therapeutic implications in a racially diverse population. (AU)