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Urinary D‐glucaric acid excretion during rifampicin/isoniazid and anticonvulsant enzyme induction
Author(s) -
Perry Wayne,
Stamp Trevor C B
Publication year - 1984
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1984.99
Subject(s) - rifampicin , excretion , isoniazid , enzyme inducer , chemistry , glucuronic acid , pharmacology , medicine , enzyme , urinary system , endocrinology , biochemistry , antibiotics , tuberculosis , polysaccharide , pathology
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 diposition of rifampicin or to genetic susceptibility to enzyme induction. Plasma β‐glucuronidase, an essential enzyme of the glucuronic acid pathway, could be induced independently of an increase in D‐glucaric acid excretion. Plasma γ‐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. Clinical Pharmacology and Therapeutics (1984) 35, 710–715; doi: 10.1038/clpt.1984.99