Chlormethiazole ethanedisulphonate (0.8%) (Hemineurin, Astra) was administered to 10 healthy unpremedicated volunteers at a constant-rate infusion of 2.5 ml/min for 60 min (Phase 1, n = 5) and 113 min (Phase 2, n = 5). With one exception, chlormethiazole blood concentration-time data were described by a two-compartment open model. Total body clearance was the same in both phases (1.151 . min-1, SD 0.49; and 1.051 . min-1, SD 0.49; and 1.051 . min-1, SD 0.36 respectively) and was similar to the clearance of indocyanine green. No correlation was found between clearance, initial dilution volume (1371, SD 62; and 1251, SD 33 in 1 and 2 phases respectively) or volume of distribution at steady-state equilibrium (3081, SD 91; and 2241, SD 59) with either body weight or estimated lean tissue mass. Slow half-life was 289 min (SD 169) in Phase 1 and 253 min (SD 172) in Phase 2. Moderately heavy sedation associated with amnesia while retaining the ability to readily obey verbal commands was achieved in one subject of Phase 1 and 4 subjects of Phase 2 and occurred at a mean chlormethiazole ethanedisulphonate blood concentration of 9.2 mg . 1(-1) (SD 2.9). Transient nasal irritation was experienced by all subjects during the initial stages of infusion. A rise in pulse rate (33%, SD 8) was a prominent feature but blood pressure and respiratory rates were very stable.
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