THE PHARMACOKINETICS AND PHARMACODYNAMICS OF ADINAZOLAM - MULTIETHNICCOMPARISONS

The pharmacokinetics and pharmacodynamics of adinazolam and N-demethyl adinazolam (NDMAD), its major active metabolite, were compared in 39 h ealthy male volunteers (13 Asian, 12 Caucasian and 14 African-American ). In a four-way, double-blind crossover design, subjects were adminis tered (1) 30 mg oral adinazolam mesylate SR tablets, (2) 10 mg parente ral (IV) adinazolam mesylate, (3) 30 mg IV NDMAD and (4) placebo. Veno us blood samples were collected at specific time intervals after drug administration and assayed for adinazolam and NDMAD concentrations. Se dation was rated at the time of each blood draw according to the Nurse -Rated Sedation Scale, and the digit-symbol substitution test was admi nistered to evaluate psychomotor performance. After IV administration of adinazolam, Asians manifested significantly higher C-max, larger AU C and lower CL of both adinazolam and NDMAD than their Caucasian and A frican-American counterparts. Likewise, after IV NDMAD Asians had sign ificantly higher NDMAD C-max and AUC than Caucasians and African-Ameri cans. Most of these differences remained statistically significant aft er controlling for body surface area. With PO adinazolam, Asians also manifested substantially higher C-max, larger AUC and lower CL for bot h adinazolam and NDMAD; however, with the exception of C-max, these di fferences did not reach statistical significance. These results are in accordance with previous observations for ethnic-related differences in drug pharmacokinetics. In contrast, pharmacodynamic differences wer e not noted among the three study groups.