Effect of carbamazepine on haem biosynthesis in man.
The effects of the enzyme-inducing anticonvulsant carbamazepine on haem biosynthesis in healthy male subjects is reported. A dose-dependent increase in the activity of leucocyte delta-aminolaevulinic-acid synthase, the rate-limiting enzyme of haem biosynthesis, was noted following 400 and 600 mg carbamazepine daily in the same eight subjects. This rise was maximal after 1 week's treatment (400 mg: 509% +/- 285 of baseline; 600 mg: 1062% +/- 170 of baseline; P less than 0.01). Values fell from this peak during the second week despite continuing carbamazepine administration. This pattern was confirmed in a further six subjects taking carbamazepine 400 mg daily for 3 weeks in whom more frequent enzyme measurements were made. The activity of uroporphyrinogen-1-synthase in the erythrocyte fell by 10-15% during the treatment periods (P less than 0.01). Uroporphyrin and penta-, hexa- and hepta-carboxylic porphyrins appeared in the urine of all subjects during CBZ therapy. Changes in daily urinary porphyrin and precursor excretion were inconsistent. CBZ is a porphyrinogenic drug which mimics the changes in enzyme activities and urinary porphyrin ester profile found in patients with latent acute intermittent porphyria, who have a genetic deficiency in uroporphyrinogen-1-synthase activity. Leucocyte delta-aminolaevulinic-acid synthase may provide a suitable in vivo system for testing the porphyrinogenicity of drugs in man.
D000624:5-Aminolevulinate Synthetase / Q000097:blood; D000328:Adult; D002220:Carbamazepine / Q000494:pharmacology*; D004912:Erythrocytes / Q000201:enzymology; D006418:Heme / Q000096:biosynthesis*; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000097:blood; D007962:Leukocytes / Q000201:enzymology; D008297:Male; D011166:Porphyrins / Q000652:urine
D011166:Porphyrins; D002220:Carbamazepine; D006418:Heme; D000624:5-Aminolevulinate Synthetase; D011163:Hydroxymethylbilane Synthase