A non-invasive method for the study of hepatic drug metabolism in rodents: antineoplastic drug effects on antipyrine metabolism in mice.

A rapid, sensitive and simple high pressure liquid chromatography (HPLC) method is described for the direct analysis of antipyrine in saliva. The detection limit was found to be 1.0 ng/ml of sample, lower than any previously reported method. Accuracy and precision were maintained with as little as 0.5 microliter of saliva. Thus the rate of elimination of antipyrine has been monitored non-invasively in rats and for the first time in mice. The antipyrine half-life was found to be 28.9 +/- 4.0 (S.E.M.) min and 111 +/- 20 min in mice and rats, respectively. In mice single i.p. doses of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) (30 mg/kg) produced increases in antipyrine half-life, up to 28 days post-treatment. The maximum effect of BCNU was observed on day 7 with an antipyrine half-life of 74.4 +/- 15.7 min. Phenobarbital induction lowered the antipyrine half-life in controls to 12.6 +/- 1.2 min. An enhanced inductive effect was observed in BCNU-treated mice: BCNU-treated, phenobarbital-induced mice displayed a half-life for antipyrine of 7.4 +/- 0.6 min on day 21 post BCNU dose. These effects could not be attributed to changes in absorption of antipyrine in BCNU-treated mice.