Effects of cimetidine on carbamazepine auto- and hetero-induction in man. 1984

G J Macphee, and G G Thompson, and G Scobie, and E Agnew, and B K Park, and T Murray, and K E McColl, and M J Brodie

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.

UI MeSH Term Description Entries
D007962 Leukocytes White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES). Blood Cells, White,Blood Corpuscles, White,White Blood Cells,White Blood Corpuscles,Blood Cell, White,Blood Corpuscle, White,Corpuscle, White Blood,Corpuscles, White Blood,Leukocyte,White Blood Cell,White Blood Corpuscle
D008297 Male Males
D002220 Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal SEIZURES. It may also be used in the management of BIPOLAR DISORDER, and has analgesic properties. Amizepine,Carbamazepine Acetate,Carbamazepine Anhydrous,Carbamazepine Dihydrate,Carbamazepine Hydrochloride,Carbamazepine L-Tartrate (4:1),Carbamazepine Phosphate,Carbamazepine Sulfate (2:1),Carbazepin,Epitol,Finlepsin,Neurotol,Tegretol
D002927 Cimetidine A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output. Altramet,Biomet,Biomet400,Cimetidine HCl,Cimetidine Hydrochloride,Eureceptor,Histodil,N-Cyano-N'-methyl-N''-(2-(((5-methyl-1H-imidazol-4-yl)methyl)thio)ethyl)guanidine,SK&F-92334,SKF-92334,Tagamet,HCl, Cimetidine,Hydrochloride, Cimetidine,SK&F 92334,SK&F92334,SKF 92334,SKF92334
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000624 5-Aminolevulinate Synthetase An enzyme of the transferase class that catalyzes condensation of the succinyl group from succinyl coenzyme A with glycine to form delta-aminolevulinate. It is a pyridoxyal phosphate protein and the reaction occurs in mitochondria as the first step of the heme biosynthetic pathway. The enzyme is a key regulatory enzyme in heme biosynthesis. In liver feedback is inhibited by heme. EC 2.3.1.37. Aminolevulinic Acid Synthetase,delta-Aminolevulinate Synthase,5-Aminolevulinate Synthase,delta-Aminolevulinic Acid Synthetase,5 Aminolevulinate Synthase,5 Aminolevulinate Synthetase,Acid Synthetase, Aminolevulinic,Acid Synthetase, delta-Aminolevulinic,Synthase, 5-Aminolevulinate,Synthase, delta-Aminolevulinate,Synthetase, 5-Aminolevulinate,Synthetase, Aminolevulinic Acid,Synthetase, delta-Aminolevulinic Acid,delta Aminolevulinate Synthase,delta Aminolevulinic Acid Synthetase
D000983 Antipyrine An analgesic and antipyretic that has been given by mouth and as ear drops. Antipyrine is often used in testing the effects of other drugs or diseases on drug-metabolizing enzymes in the liver. (From Martindale, The Extra Pharmacopoeia, 30th ed, p29) Phenazone,Anodynin,Pyramidone
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

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