The pharmacokinetics of chlormethiazole following intravenous administration in the aged

Abstract

Eight healthy aged subjects were administered 1.2 g of chlormethiazole by constant-rate intravenous infusion. The disposition of the drug was found to be multi-exponential in character. Fits of plasma level-time data to two- and three-compartment open models were assessed with the aid of statistical tests. For three of the subjects the experimental data were adequately fitted to a two-compartment pharmakcokinetic model, however a three-compartment model was necessary to fit the data observed for a further four subjects. An anomalous chlormethiazole plasma concentration-time curve was obtained for the remaining subject. The disposition half-life of chlormethiazole was 8.49 +/- 3.28 h and the plasma clearance was 16.14 +/- 5.00 ml/min/kg. These values were significantly different to those reported earlier for young adult subjects and the clinical implications have been discussed. The blood/plasma concentration ratio of chlormethiazole was found to be approximately one with some evidence for concentration dependence.