The effects in man of liver disease, renal failure and hepatic microsomal enzyme induction on the elimination kinetics of antipyrine in saliva have been examined. Antipyrine (10 mg/kg) was given orally and assayed in saliva by gas-liquid chromatography. The mean antipyrine half-life from saliva in nine epileptic subjects receiving long term anticonvulsant drug therapy (6 hr +/- 0-9 SEM) was significantly shorter than in twenty normal healthy volunteers (10-7 +/- 0-6). Therapy included phenytoin and phenobarbitone, two drugs known to induce hepatic microsomal enzymes. Five subjects with chronic renal failure exhibited no significant difference in salivary anti-pyrine half-life (11-7 +/- 1-9) compared to the control group, whereas six subjects with chronic liver disease and impaired hepatic function had significantly increased half-life values (42-4 +/- 10). The results suggest that differences in the activity of hepatic microsomal enzymes are reflected by changes in salivary antipyrine elimination kinetics. Chronic renal failure appeared to have no effect on the function of these enzymes.

Antipyrine kinetics were measured on saliva in eight anaesthetists during a period when they were giving general anaesthetics and a period when they were working exclusively in intensive care. During the anaesthesia period there was a reduction in antipyrine half-life and the clearance of antipyrine increased. A nalysis of the data in groups failed to detect these changes because of the wide variation in metabolism between subjects. Exposure to anaesthetic agents under non-scavenging operating theatre conditions appears to enhance hepatic metabolism.

1The effects of chronic ethanol intake on the elimination kinetics of antipyrine were determined in nineteen male alcoholic subjects with comparison made to fourteen male volunteers. 2 Half-lives were longer and clearance values less in the alcoholic group. 3 Significant rank correlations were found between half-life and clearance when compared with various biochemical parameters of liver function measured in the plasma of the alcoholics. 4 These results show that a significant proportion of the alcoholics studied had impaired hepatic drug metabolizing capacity and that the activity of hepatic microsomal enzymes may be related to the extent of ethanol induced liver damage in these subjects.