Serum concentration of chlormethiazole and therapeutic effect in acute alcohol withdrawal syndrome: an open clinical trial.
It was the aim of this study to find a relationship between the serum concentration of chlormethiazole and its therapeutic effect in acute alcohol withdrawal syndrome. As a secondary subject, the concentration of chlormethiazole was investigated in relation to variables of treatment and variables of physical status of patients. In an open clinical trial, the clinical status of patients was rated by the Mainz Alcohol Withdrawal Scale (MAWS) and the Delirium Rating Scale (DRS). Chlormethiazole concentration was measured by gas-liquid chromatography. Patients were dichotomized according to minimum values of MAWS and DRS after 2 days of treatment (good response and retarded or no response). Chlormethiazole concentration and dose per body weight and MAWS and DRS scores before treatment were compared by the Student t test and the Mann-Whitney test. The two groups were also analyzed by logistic regression with chlormethiazole concentration, MAWS and DRS score before treatment, age, gender, body weight, years of alcoholism, and dose per body weight as independent variables. Chlormethiazole concentration was analyzed by multiple regression with dose, age, gender, smoking, initial alcohol, body weight, and liver dysfunction as independent variables. Forty-three patients were included in the study. Twenty-four patients reached a minimum time of investigation of 2 days. The chlormethiazole concentration was in the range of 0.3 to 5.4 microg/mL at doses of 10 to 24 capsules/d (1 capsule = 192 mg chlormethiazole). As the main result, significantly increased chlormethiazole concentrations were found in patients with retarded or no response; however, in addition the DRS score before treatment and dose per body weight were increased. In addition, the final models of logistic regression contained only DRS score before treatment. As a secondary result, the final model of multiple regression revealed an increased chlormethiazole concentration with dose of chlormethiazole and concentration of alcohol in blood and a decreased chlormethiazole concentration with body weight. This was the first study to investigate the relationship between the chlormethiazole concentration and therapeutic effect in alcohol withdrawal. No robust relationship could be detected that could be separated from the control of treatment by clinical variables. Rather, a poor therapeutic outcome is mainly predicted by an increased initial severity of symptoms, and higher doses are applied in more severely ill patients. Thus, pharmacokinetic control of treatment is not recommended.
Ulrich
Sven
S
Institute of Clinical Pharmacology, University Hospital, Otto-von-Guericke University, Leipziger Strasse 44, D-39120 Magdeburg, Germany. sven.ulrich@medizin.uni-magdeburg.de
Danos
Peter
P
Baumann
Bruno
B
Müller
Dörthe
D
Lehmann
Dörthe
D
Treuheit
Tim-Oliver
TO
Spieler
Marion
M
D000208:Acute Disease; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D002719:Chlormethiazole / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000473:pathology
D000927:Anticonvulsants; D002719:Chlormethiazole; D000431:Ethanol