Kinetics of intravenous chlordiazepoxide: Sex differences in drug distribution

Fourteen healthy subjects (7 male and 7 female) received 50 mg of chlordiazepoxide (CDX) hydrochloride by I‐hr intravenous infusion. Multiple venous blood samples drawn during the 72 hr after the infusion were assayed for whole blood concentrations of CDX and of its major metabolite, desmethylchlordiazepoxide (DMCDX). Mean (±SE) pharmacokinetic parameters, determined by weighted nonlinear least‐squares regression analysis, were: distribution half‐life, 1.3 (±0.3) hr; elimination half‐life, 17.8 (±2 .2) hr; volume of central compartment (VI), 0.27 (±0.02) Llkg; total distribution space (V.J, 0.52 (±0.03) Llkg; total clearance, 26.4 (±3.2) mllmin. Viand Vd were significantly larger among females (0.30 and 0.58 Llkg) than among males (0.22 and 0.45 Llkg), suggesting more extensive drug distribution in females. Values of half‐life and of clearance did not, however, differ significantly between sexes. A second study in three subjects compared simultaneous whole blood and plasma CDX concentrations after intravenous bolus injection and showed them to be highly correlated. Red cell :plasma partition ratios were 0, O.OJ, and 0.24, indicating limited uptake of CD X by red cells. Volumes of distribution and clearances calculated from CDX concentrations in whole blood are larger than those based on plasma concentrations.