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Influence of rifampicin treatment on antipyrine clearance and metabolite formation in patients with tuberculosis.
Author(s) -
Teunissen MW,
Bakker W,
MeerburgTorren JE,
Breimer DD
Publication year - 1984
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1984.tb02532.x
Subject(s) - rifampicin , pyrazinamide , metabolite , chemistry , pharmacology , volume of distribution , isoniazid , metabolism , pharmacokinetics , drug metabolism , cytochrome p450 , enzyme inducer , medicine , tuberculosis , endocrinology , enzyme , biochemistry , antibiotics , pathology
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.