The pharmacokinetics of clonidine in high dosage.

We have evaluated the pharmacokinetics of high doses of clonidine, as used in the prophylactic treatment of alcohol withdrawal syndrome, in 11 alcohol-dependent patients undergoing surgery for oesophagogastrectomy. Clonidine was given in a bolus of 150 micrograms followed by a continuous infusion. After a mean period of treatment of 9.2 (range 3 to 26) days and a mean dose of 0.72 (range 0.29 to 2.37) mg per day of clonidine the mean terminal half-life was 15.8 (range 9.9 to 23) h (n = 7). In order to compare initial and terminal half-lives of clonidine intraindividually, four patients were given a bolus of 150 micrograms followed 24 h later by a continuous infusion. The pharmacokinetics of clonidine were described by two exponentials, with a distribution half-life of 1.2 h and a terminal half-life of 14.6 h. After a mean period of 8.3 (range 2 to 15) days and a mean dose of 0.62 (range 0.15 to 1.82) mg per day the terminal half-life in these four patients was 15.6 (range 14.0 to 17.9) h. The relation between dosage and plasma concentration was linear.