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.

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A patient with atypical bilateral facial pain reported the loss of analgesic effect of intracerebroventricular morphine delivered continuously via an implanted pump, accompanied by intolerable adverse side effects associated with the administered high dose of morphine. Clonidine was substituted for morphine over a period of 3 weeks to achieve a drug holiday. The patient did not have significant withdrawal symptoms or major discomfort from pain, leading to a reduced quality of life during this period. Six months after the treatment, the patient continues to require a significantly lower daily dose of morphine. Morphine withdrawal with clonidine substitution produced a significant improvement in the analgesic efficacy of morphine and in the quality of life in the absence of undesirable side effects.

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