Alteration of warfarin kinetics in man associated with exposure to an operating-room environment

The plasma half-life of warfarin (mean +/- SE) in five normal, nonmedicated control subjects given a single 40 mg/m2 oral dose of warfarin was 38.8 +/- 4.1 hours. It was essentially the same (37.7 +/- 2.6 hours) in these subjects when determined again four months later. The effect of the single dose of warfarin on prothrombin complex activity (prothrombin response) was determined by calculating the area under the curve obtained by plotting prothrombin time (seconds) versus time after the warfarin dose (hours). The prothrombin response in control subjects was 1670 +/- 64 sec-hr initially and essentially the same at the end of the four-month interval (1730 +/- 96 sec-hr). Plasma warfarin half-life and prothrombin response in seven anesthesiology residents were 32.1 +/- 3.6 hours and 1337 +/- 78 sec-hr at the start of their training period, i.e., before working in the operating room. Four months later, their plasma warfarin half-lives were significantly prolonged (49.3 +/- 4.8 hours) and the prothrombin responses were significantly greater (1552 +/- 22 sec-hr) compared with their initial values. The alteration of warfarin kinetics appeared to be due mainly to inhibition of warfarin metabolism, presumably related to the repeated exposure of these subjects to an operating room environment.