Effect of carbamazepine on haem biosynthesis in man

Publisher Website
Google Scholar
Abstract
Summary. 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 δ‐aminolaevulinicacid 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 < 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 < 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 δ‐aminolaevulinic‐acid synthase may provide a suitable in vivo system for testing the porphyrinogenicity of drags in man.