Influence of rifampicin treatment on antipyrine clearance and metabolite formation in patients with tuberculosis.
The influence of an 8-day therapy with rifampicin (600 mg daily) was studied on antipyrine plasma clearance and metabolite formation in seven patients with tuberculosis (age 18-79 years), who were also treated with isoniazid and pyrazinamide. After rifampicin treatment the elimination half-life of antipyrine had decreased in all patients from 12.9 +/- 5.0 to 8.8 +/- 2.0 h (P less than 0.05). Antipyrine clearance had increased from 2.2 +/- 0.9 to 2.9 +/- 0.7 l/h (P less than 0.05), while no change in apparent volume of distribution was observed. The increase in antipyrine clearance was primarily due to a selective increase in the rate of formation of norantipyrine by 80% from 6.9 +/- 3.4 to 12.4 +/- 3.4 ml/min. Rifampicin seems to induce preferentially the cytochrome P-450 (iso-) enzyme(s) involved in the demethylation of antipyrine to norantipyrine. Other pathways of antipyrine metabolism were hardly affected. This provides further evidence for the involvement of different iso-enzymes of the cytochrome P-450 system in antipyrine metabolism in man.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000983:Antipyrine / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged; D012293:Rifampin / Q000494:pharmacology*; D014397:Tuberculosis, Pulmonary / Q000378:metabolism*
D000983:Antipyrine; D012293:Rifampin