Diazepam effects and kinetics in Caucasians and Orientals

Abstract

Mental and psychomotor effects and diazepam kinetics were studied in Caucasian and Orientals. 12 Caucasian and 13 Oriental young adults received on one of two occasions, separated by 2 weeks, either 0.2-mg/kg diazepam or saline intravenously. Serum diazepam and desmethyldiazepam concentrations were measured by electron-capture gas-liquid chromatography in samples drawn up to 72 hr after injection. Serum protein binding was measured by equilibrium dialysis. Subjects were tested on a battery of psychological tests before and 0.5, 2, and 4 hr after treatment. While the free fraction of diazepam was identical in both races (0.02), volume of distribution at steady state (Vdss) was different when calculated as absolute volume (Vdss = 76.55 +/- 9.63 l in Caucasians and 54.96 +/- 4.55 l in Orientals, p = 0.04) and marginally significant when corrected for body weight (Vdssl/kg = 1.10 +/- 0.11 in Caucasian and 0.88 +/- 0.05 in Orientals, p = 0.07). total body clearance (Cl), but not elimination half-life (t 1/2), was higher in Caucasians than Orientals, p less than 0.01; t 1/2 = 37.70 +2- 5.53 hr in Caucasians and 41.77 +/- 3.80 in Orientals). Desmethyldiazepam levels were higher in Orientals than Caucasians. Mental and psychomotor effects were maximal at the first session (0.5 hr), followed by complete recovery by the 4-hr session. Effects were similar in both groups. If repeated dosing causes a higher rate of cumulated diazepam serum levels in Orientals, as expected, there might be deeper brain depression in that group.