Effect of the cardiopulmonary bypass procedure during cardiac surgery on CYP2C9 activity in human

Abstract

Clinical observations suggest that warfarin sensitivity is increased in patients undergoing cardiac surgery that involves a cardiopulmonary bypass (CPB) procedure. Factors such as hemodilution, altered plasma protein binding or change in visceral perfusion during CPB may cause changes in pharmacokinetic parameters of various drugs. Since CYP2C9 is the major enzyme that metabolizes warfarin, we aimed to investigate if the increase in warfarin sensitivity was associated with inhibition of the activity of this individual enzyme due to CPB in human. Losartan oxidation to E3174 was used as a marker for CYP2C9 activity. Urinary losartan/E3174 ratios after a single 25 mg oral dose were measured in 23 patients at three occasions: at the baseline, and on the first and fifth postoperative days. The average metabolic ratio (median, range) was significantly increased for about 3.3 fold as compared to the baseline value (0.84, 0.1–7.94 vs. 2.80, 0.7–278.2) in the acute phase immediately after the surgery (P=0.01). The metabolic ratio returned to the baseline value when measured at the fifth postoperative day (P=0.24). These results suggest that CYP2C9 metabolic activity is inhibited at the very early stage of postoperative period and recovers as early as within five days in patients that undergo cardiac surgery with a cardiopulmonary bypass procedure. (Supported by TUBITAK-SBAG COST B25-105S027 and UY/TUBA-GEBIP/2005-17)