EFFECT OF CARDIOPULMONARY BYPASS ON PLASMA-CONCENTRATIONS OF DILTIAZEM AND ITS 2 ACTIVE METABOLITES

Diltiazem is often used to prevent myocardial ischaemia during the per ioperative period of coronary artery bypass surgery. The purpose of th is study was to investigate the effect of cardiopulmonary bypass (CPB) on plasma concentrations of diltiazem and of its two main and active metabolites (N-monodemethyldiltiazem (N-desmethyldiltiazem) and desace tyldiltiazem). The patients were administered their usual treatment du ring the preoperative days. The last dose was administered immediately before anaesthesia. At the onset of CPB, a significant decrease in th e plasma concentrations of diltiazem and its metabolites was observed, whereas the variation was slight and not significant when the plasma concentrations were corrected for haemodilution. These results confirm that the decrease observed at the initiation of the bypass procedure can be ascribed to the haemodilution induced by the CPB. During CPB, t he concentrations of diltiazem and its metabolites remained constant s uggesting that the rate of metabolism and excretion of the drug was al tered during the bypass procedure. At the end of CPB, there was no inc rease of drug plasma concentrations suggesting that no redistribution of diltiazem from tissues to plasma occurred. Furthermore, this study shows that only 33% of subjects have therapeutic levels of diltiazem b efore anaesthesia, and that all subjects have subtherapeutic levels du ring and after the CPB. These results suggest that a higher chronic or al dose of the drug should be given in patients undergoing cardiac sur gery with CPB.