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Effects of cimetidine on carbamazepine auto‐ and hetero‐induction in man.
Author(s) -
Macphee GJ,
Thompson GG,
Scobie G,
Agnew E,
Park BK,
Murray T,
McColl KE,
Brodie MJ
Publication year - 1984
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1984.tb02483.x
Subject(s) - cimetidine , carbamazepine , pharmacology , medicine , anticonvulsant , anesthesia , epilepsy , psychiatry
The effect of cimetidine (CMT; 400 mg twice daily) and matching placebo on the enzyme‐inducing properties of carbamazepine (CBZ; 200 mg at night for 15 days) was studied in seven healthy male volunteers. CMT alone had no significant effect on antipyrine kinetics, urinary 6 beta‐ hydroxycortisol excretion or leucocyte delta‐aminolaevulinic acid synthase (ALA.S) activity. CBZ increased leucocyte ALA.S activity by 204% following 1 week's treatment (P less than 0.001). Thereafter, ALA.S activity fell despite continued CBZ administration. Concomitant CMT did not influence this response. Antipyrine clearance and urinary 6 beta‐hydroxycortisol excretion were both increased by CBZ after 2 weeks' treatment (P less than 0.01). CMT blocked CBZ induction of antipyrine metabolism but the rise in urinary 6 beta‐hydroxycortisol excretion was unaffected. Plasma CBZ concentrations 10, 14 and 18 h following the 8th and 15th doses were higher when CMT was taken concurrently (P less than 0.05). CBZ half‐life fell by 36% and clearance rose by 29% (both P less than 0.001) with placebo and by 10% and 7% (both NS) when CMT was taken concurrently. CMT inhibits CBZ auto‐ and hetero‐induction in man. Epileptic patients receiving CBZ chronically may be at risk of toxicity if CMT is also prescribed.