The Plasma Half-life of Antipyrine in Chromic Uraemic and Normal Subjects

1. Antipyrine was given intravenously in a dose of 18 mg/kg body weight to twelve patients with chronic renal failure (plasma creatinine greater than 4.9 mg/100 ml) who were not taking drugs and twenty normal subjects. 2. Plasma antipyrine levels were measured by a specific method, the plasma half-life of the drug was determined and used as an index of drug oxidation. 3. The mean (+/- s.d) plasma antipyrine half-life in patients with chronic renal failure (7.3 +/- 2.0 h) was significantly shorter than in normal subjects (13.2 +/- 4.3 h: P less than 0.002). There was no difference in the apparent volume of distribution of antipyrine between the two groups (P greater than 0.6). 4. Pretreatment of five patients with chronic renal failure and seven normal subjects with antipyrine or phenobarbitone for weeks significantly shortened the mean plasma antipyrine half-life from 7.4 +/- 2.5 h to 5.0 +/- 1.5 h in uraemics (P less than 0.005) and from 13.2 +/- 4.5 h to 6.9 +/- 1.5 h in normal subjects (P less than 0.0025).5. These results suggest that oxidation of antipyrine by hepatic microsomal enzymes is increased in patients with chronic renal failure, but a state of maximal induction of these enzymes was not observed. The clinical implication of this finding with regard to the association between liver microsomal enzyme induction and vitamin D resistant osteomalacia is discussed.