The plasma half‐life of antipyrine in chromic uraemic and normal subjects.

Abstract

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.

Analysis of Polymorphonuclear Leukocyte Respiratory Burst Activity in Uremic Patients using Whole-Blood Chemiluminescence

“…Another complicating factor is the observation that many enzymes show increased activity in chronic (but not acute) renal failure [29], including those enzymes in volved in the respiratory burst of phagocytic cells [II]. Such an adaptive enzyme induction could account for the small but statistically significant increase in respiratory burst activity observed for uremic blood PMNL in this study.…”

Pharmacokinetics of Drugs in Rabbits with Experimental Acute Renal Failure

“…For aminophenazone (14), pentobarbital (24), phenacetin (21) and tolbutamide (9), the halflife was found to be unchanged. For antipyrine (16,18), phenylbutazone (10,14) and propran olol (3,17,27), contradictory results were obtained. There has also been a study in rabbits with acute renal failure, where a slower decline in blood levels o f thiopental was found (25).…”

“…The changes in half-life found in man or in animals are often explained by changes in he patic metabolism (1,10,14,15,18,20,25,27), but in vitro studies showed a tendency to a decrease in activity o f the hepatic microsomal enzymes in rats with acute renal failure (12,13,19,28). However, the possibility that in some instances, the half-life is shortened by the decreased serum protein binding in renal failure (2, 23) has been forwarded (10,15,20).…”

Enhanced drug metabolism and renal dysfunction.

“…Increased drug metabolism due to enzyme induction might also be a mechanism underlying the above findings in patients with impaired renal function, since the plasma antipyrine half-life, an index of the drug metabolizing capacity of the liver (Vessell & Page, 1968), is diminished in chronic renal failure (Maddocks, Wake & Harber, 1975). In favour of this assumption further evidence was obtained in our recent studies performed in children with mild renal dysfunction.…”