Urinary D-glucaric acid excretion during rifampicin/isoniazid and anticonvulsant enzyme induction.
As measured by urinary D-glucaric acid excretion, an index of hepatic enzyme induction, glutethimide was the most powerful of six such inducers tested. In patients with tuberculosis, rifampicin, 450 mg daily, induced excretion rates of the lower dose range of anticonvulsants in epileptics. The effect was detectable in the first few days but the degree and rate of rise to maximum excretion were variable. This may be due either to disposition of rifampicin or to genetic susceptibility to enzyme induction. Plasma beta-glucuronidase, an essential enzyme of the glucuronic acid pathway, could be induced independently of an increase in D-glucaric acid excretion. Plasma gamma-glutamyltranspeptidase-levels, an index of hepatic microsomal enzyme induction, were elevated in only 20 of 83 subjects receiving rifampicin and isoniazid, and in all of them urinary D-glucaric acid excretion was normal. Neither of these indices, therefore, showed hepatic enzyme induction during combined therapy when other pathways such as oxidative metabolism continued to be induced. Different active sites of rifampicin and isoniazid on glucuronic acid and other biochemical pathways emphasize the complexity of final metabolic effects in patients on long-term therapy.
D000293:Adolescent; D000328:Adult; D000368:Aged; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005937:Glucaric Acid / Q000652:urine*; D005966:Glucuronidase / Q000096:biosynthesis*; D005984:Glutethimide / Q000494:pharmacology; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology*; D013400:Sugar Acids / Q000652:urine*; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis
D013400:Sugar Acids; D010672:Phenytoin; D005984:Glutethimide; D005723:gamma-Glutamyltransferase; D005966:Glucuronidase; D005937:Glucaric Acid; D007538:Isoniazid; D012293:Rifampin