The pharmacokinetics of chlorbutol in man

The pharmacokinetics of chlorbutol were studied after oral administration in 4 healthy subjects on two occasions. Following the rapid attainment of peak concentrations, plasma concentrations fell by approximately 50 per cent in 24 h. After the first dose of chlorbutol, the terminal elimination half-life was 10.3 +/-1.3 days (mean +/- S.E.M), the volume of distribution was 233 +/- 141 and the plasma clearance was 11.6 +/- 1.0 ml min-1. The binding to plasma proteins was 57 +/- 3 per cent. In 3 of the 4 subjects, there was a small but significant decrease in the terminal half-life of chlorbutol after the second dose. The mean urinary recovery over 17 days in two of the subjects accounted for only 9.6 per cent of the dose, 7.4 per cent of the total as the glucuronide and sulphate conjugates and 2.2 per cent as unchanged chlorbutol. A significant factor in the elimination of chlorbutol may be its instability under physiological conditions. Its half-life in vitro is 37 days at pH 7.4. The long terminal half-life of chlorbutol makes it unsuitable as a sedative drug because of the considerable accumulation which will occur when the drug is taken in multiple doses.