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. 1984 Sep;18(3):411–419. doi: 10.1111/j.1365-2125.1984.tb02483.x

Effects of cimetidine on carbamazepine auto- and hetero-induction in man.

G J Macphee, G G Thompson, G Scobie, E Agnew, B K Park, T Murray, K E McColl, M J Brodie
PMCID: PMC1463645  PMID: 6487479

Abstract

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.

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Selected References

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