The plasma levels of chlormethiazole and two of its metabolites in elderly subjects after single and multiple dosing.
Plasma levels of chlormethiazole and two of its metabolites have been estimated in elderly subjects both after single and repeated oral dosage and on withdrawal. A sensitive analytical method was developed to permit the quantitation of chlormethiazole and its two major metabolites in plasma. The two major metabolites were positively identified against authentic standards as 5-acetyl-4-methylthiazole and 5-(1-hydroxyethyl)-4-methylthiazole. Chlormethiazole and its metabolites were shown to have accumulated to varying extents after seven nightly doses. On withdrawal of the drug, the plasma was free of chlormethiazole within 44 h and free of all traces of its metabolites within 84 h. The accumulation was not accompanied by any undue clinical effect and was not in itself considered to be detrimental to the normal use of chlormethiazole in the treatment of sleep disturbances in the elderly.
Witts
D J
DJ
Departments of Clinical Pharmacology and Geriatric Medicine, University College Hospital Medical School, London WC1, UK.
Arnold
K
K
Exton-Smith
A N
AN