Sir: A 42-year-old man, weighing 100 kg, was admitted to the hospital at 07.00 hours to undergo eyelid surgery under local anaesthesia. He was given clorazepate 100 mg at 08.00 hours. When he arrived in the operating room he was unconscious (Glasgow score used to assess the consciousness was 11 (normal score: 15)). The cooperation of the patient was necessary to perform this surgery. The patient was then given a bolus of flumazenil (0.5 mg intravenously (i.v.)) to reverse effects of clorazepate followed by an infusion (1 μg kg−1 h−1) of flumazenil to obtain an acceptable level of consciousness (Glasgow = 14). The infusion was stopped 28 h later but the patient did not completely wake up until 36 h after the oral administration (Glasgow = 15). The pre-operative patient interview had shown that he had been treated for a long time for a psychiatric disorder with Paroxetine 20 mg and Phenothiazine 25 mg daily. The patient took his daily dose before his arrival. No detectable liver or renal abnormalities were found. Plasma concentrations of the main metabolite (N-desmethyldiazepam) were measured by a high pressure chromatographic method, and were 400, 540 and 505 ng mL−1 respectively, 28, 40 and 52 h after administration.
First, these concentrations are lower than those previously reported [1,2] with the equivalent doses. The patient was sleeping with a low concentration of desmethyldiazepam and awoke with about the same concentration. This fact suggests that there is no relation between plasma concentration and neurological effects.
Second, the dose of clorazepate administered here (1 mg kg−1) was very high. We advise using a benzodiazepine with a short elimination half-time for out-patients or a dose of clorazepate very much lower than 1 mg kg−1.
E. CALENDA, M. MURAINE and N. PROUST
Centre Hospitalier Universitaire de Rouen, Rouen, France
1 Bertler A, Lindgren S, Malmgren H. Pharmacokinetics of dipotassium clorazepate in patients after repeated 50 mg oral doses. Psychopharmacology
2 Aymard Nicolle. Analyse pharmacocinétique d'une benzodiazepine, le clorazepate dipotassique. Psychologie mé dicale
A 'hors série': 145–154.