Differential Effects of Isoniazid and Oral Contraceptive Steroids on Antipyrine Oxidation and Acetaminophen Conjugation

Factors influencing hepatic oxidation of antipyrine and conjugation of acetaminophen were evaluated in volunteers who received 1.0 g of antipyrine intravenously and on a different occasion a 650 mg intravenous dose of acetaminophen. In study one, subjects received both drugs in the control state and at another time during coadministration of isoniazid (INH), 180 mg daily. In control versus INH conditions, mean clearance of antipyrine was reduced from 0.67 to 0.60 ml/min/kg as was clearance of acetaminophen from 4.97 to 4.23 ml/min/kg, but these differences were not statistically significant. In study two, females on low-dose estrogen oral contraceptives (OC) and drug-free controls matched for age received both drugs. Compared to controls, OC users had reduced total clearance of antipyrine (0.71 vs. 0.50 ml/min/kg; p less than 0.005) and prolonged antipyrine t1/2 (9.6 vs. 13.3 h; p less than 0.005). For acetaminophen, however, OC users had higher clearance (5.2 vs. 6.1 ml/min/kg) and shorter t1/2 (2.2 vs. 1.9 h) although differences did not attain statistical significance. Clearance of antipyrine and acetaminophen across both studies was not statistically significantly correlated within individuals (r = 0.22). The capacities for drug oxidation and conjugation appear to be controlled by different mechanisms.