EFFECTS OF HEME ARGINATE ON CYTOCHROME-P450 - MEDIATED METABOLISM OF DRUGS IN PATIENTS WITH VARIEGATE PORPHYRIA AND IN HEALTHY-MEN

We investigated the effects of heme on metabolism of coumarin, debriso quin, caffeine, and lidocaine in seven female patients with variegate porphyria and in 10 healthy men. During baseline conditions metabolism of the drugs was identical in the two groups. Compared with the resul ts without heme, a single infusion of heme arginate (3 mg/kg heme) sig nificantly decreased the debrisoquin/4-hydroxy-debrisoquin metabolic r atio in subjects with porphyria (p = 0.016) and in the control subject s (p = 0.016) and increased formation of monoethylglycinexylidide from lidocaine (P = 0.016 and p = 0.004, respectively). Metabolism of coum arin and caffeine was not affected by heme. Our results show that, in patients with porphyria and in healthy subjects, exogenous heme is abl e to accelerate the reactions mediated by the cytochrome isozymes CYP2 D6 (debrisoquin) and CYP3A4 (lidocaine) but not reactions mediated by CYP1A2 (caffeine) and CYP2A6 (coumarin). This suggests that influence of heme on drug metabolism is P450 isozyme-specific.