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.

Keywords:

• Cardiopulmonary bypass
• cardiac surgery
• cytochrome P450
• pro-inflammatory cytokines
• pharmacokinetics

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

J. F. F. acknowledges fellowship from the Office of Health and Medical Research, Queensland Government, Australia. SG and CIPDD are supported financially by Therapeutic Innovation Australia (TIA). TIA is supported by the Australian Government through the National Collaborative Research Infrastructure Strategy (NCRIS) program. S. A. received International Postgraduate Research Scholarship (IPRS) and University of Queensland Centennial Scholarship (UQCent).