Papers and Originals
BRITISH MEDICAL JOURNAL 19 FEBRUARY 1972 463 PAPERS AND ORIGINALS Drug Interaction: Inhibitory Effect of Neuroleptics on Metabolism of Tricyclic Antidepressants in Man LARS F. GRAM, KERSTIN FREDRICSON OVERO British Medical Journal, 1972, 1, 463-465 excretion (Anders, 1971). There are relatively few reports on interaction concerning neuroleptics or tricyclic antidepressants. Summary Chlorpromazine has both stimulatory and inhibitory effects on the metabolism of hexobarbitone in Total urinary excretion of radioactivity after oral or experimental animals of a test of (Riimke and Bout, 1960-1). Furthermore, chlorpromazine intravenous administration dose '4C-imi- accelerates the metabolism pramine was measured in were tested ofmeprobamate (Kato and Vassanelli, eight patients. They 1962). Tricyclic antidepressants have been shown to inhibit the before, during, and after treatment with neuroleptics. metabolism Excretion diminished while the were of tremorine and oxotremorine in rats in vitro and patients being in vivo (Hammer and Sjoqvist, 1967). It has also been found treated with perphenazine, haloperidol, or chlorproma- that zine, not treatment. desipramine hydrochloride inhibits the metabolism of though during flupenthixol amphetamine in isolated, perfused rat liver (Dingell and Bass, Total urinary excretion of radioactivity and plasma 1969). Pretreatment levels of metabolites and were measured with phenobarbitone decreased steady-state unchanged drug plasma levels of desipramine and nortriptyline in man (Sjoqvist in five patients after a test dose of 14C-nortriptyline. Each et was before and al. 1968). These findings were later confirmed in a twin study patient tested again during perphenazine (Alexanderson et al., 1969). Forrest et treatment. In all patients perphenazine treatment caused: al. (1970) found increased (1) decrease of total urinary excretion, (2) decreased urinary excretion of chlorpromazine metabolites when patients plasma level of metabolites, and (3) increased plasma were given additional treatment with phenobarbitone.
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