Effect of cardiopulmonary bypass on cytochrome P450 enzyme activity: implications for pharmacotherapy

Abstract

For patients undergoing cardiopulmonary bypass (CPB) during cardiac surgery, there are well-documented changes in the pharmacokinetics (PK) of commonly administered drugs. Although multiple factors potentially underpin these changes, there has been scant research attention on the impact of CPB to alter the activities of cytochrome P450 (CYP) isoenzymes. PK changes during cardiac surgery with CPB have the potential to adversely affect the safety and efficacy of pharmacotherapy and increase the risk of drug-drug interactions. Clinically significant changes in drug PK during CPB are likely to be prominent for drugs where CYP metabolism is a major clearance (CL) mechanism. However, clinical data from patients undergoing CPB surgery in support of this hypothesis are lacking, leaving a significant knowledge gap. In this review, we address the effects of CPB on the release of pro-inflammatory cytokines, in surgeries with and without CPB, both pre and post initiation of surgery. We reviewed literature to explore the relationship between the release of pro-inflammatory cytokines, and the expression and activities of CYP enzymes. Through this approach, we provide new insight on the effects of CPB on the PK of drugs administered to patients in the clinical setting. Future research to address this knowledge gap will have considerable impact to assist clinicians with optimizing pharmacotherapy in this patient population.

Study Protocol for a Pilot, Open-Label, Prospective, and Observational Study to Evaluate the Pharmacokinetics of Drugs Administered to Patients during Extracorporeal Circulation; Potential of In Vivo Cytochrome P450 Phenotyping to Optimise Pharmacotherapy

“…In other work, the plasma concentrations of the major anti-inflammatory cytokine, IL-10, were significantly higher in the broncho alveolar lavage fluid of VV-treated animals [10]. There are several examples in the clinical literature whereby cytokines have been implicated in altering cytochrome P450 (CYP) isoenzyme activities during cardiopulmonary bypass [11] resulting in impaired metabolism of clinically important drugs leading to their accumulation in the body and potential the potential for causing adverse effects.…”

“…These effects constantly change during surgeries using CPB and some continue to exert their influence after the patient has been successfully separated from CPB. Drugs that have critical roles in determining patients’ health and surgical outcomes such as anaesthetics, opioid analgesics, neuromuscular blockers, and antibiotics, are reportedly affected during and after surgery using CPB [11].…”