Pharmacokinetics of midazolam in Vietnamese subjects

In order to examine the investigators' clinical suspicion that Vietnamese patients were more sensitive to the sedative effects of midazolam than were Caucasians, the pharmacokinetics of a single, weight-adjusted intravenous dose of midazolam (0.05 mg/kg) were compared in a group of healthy Caucasian and Vietnamese male volunteers. The Vietnamese group (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 the Caucasian group (n = 8). No significant differences were found between the Vietnamese and Caucasian groups with regard to distribution half-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, respectively), clearance (4.93 +/- 1.31 vs 5.90 +/- 2.12 mL/min per kg, respectively), 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 dosage of midazolam in Vietnamese should be based on total bodyweight. Two Vietnamese subjects who were brothers had marked elevation of distribution half-life and initial volume of distribution and lesser elevations in elimination half-life and volume of distribution at steady state. This suggests that the known subgroup of subjects who demonstrate dyshomogeneity in midazolam volume of distribution may be genetically determined.