PHARMACOKINETICS OF MIDAZOLAM IN VIETNAMESE SUBJECTS

In order to examine the investigators' clinical suspicion that Vietnam ese patients were more sensitive to the sedative effects of midazolam than were Caucasians, the pharmacokinetics of a single, weight-adjuste d intravenous dose of midazolam (0.05 mg/kg) were compared in a group of healthy Caucasian and Vietnamese male volunteers. The Vietnamese gr oup (n = 8) had a significantly lower height, lean body mass and mean weight (59.8 +/- 5.5 vs 72.1 +/- 8.1 kg, respectively) compared with t he Caucasian group (n = 8). No significant differences were found betw een the Vietnamese and Caucasian groups with regard to distribution ha lf-life of midazolam (8.38 +/- 13.1 vs 1.49 +/- 0.63 min, respectively ), elimination half-life (2.49 +/- 1.80 vs 1.48 +/- 0.66 h, respective ly), clearance (4.93 +/- 1.31 vs 5.90 +/- 2.12 mL/min per kg, respecti vely), steady state volume of distribution (0.863 +/- 0.497 vs 0.530 /- 0.132 L/kg, respectively) or percentage of unbound drug in plasma ( 4.89 +/- 0.74 vs 4.11 +/- 1.08, respectively). This suggests that dosa ge of midazolam in Vietnamese should be based on total bodyweight. Two Vietnamese subjects who were brothers had marked elevation of distrib ution half-life and initial volume of distribution and lesser elevatio ns in elimination half-life and volume of distribution at steady state . This suggests that the known subgroup of subjects who demonstrate dy shomogeneity in midazolam volume of distribution may be genetically de termined.