CYP2C9-dependent variability in propofol pharmacokinetics and hemodynamic effects: A population-based pharmacogenetic...

Propofol is a key anesthetic whose use is complicated by significant variability in patient response. This study highlights the influence of CYP2C9 variants rs1799853/*2 and rs1057910/*3 on propofol serum concentration and clearance, as well as the hemodynamic changes induced by this drug. For this cross-sectional pharmacogenetic study, 250 Pakistani patients undergoing elective surgeries under general anesthesia with propofol were recruited. Baseline parameters, along with pre- and post-induction mean blood pressure (MBP) and heart rate (HR), were recorded. The patients were genotyped for the CYP2C9 polymorphisms (rs1799853/*2 and rs1057910/*3) using the ARMS PCR technique. Serum propofol levels were measured at 5 and 10 min after induction. Based on their serum levels, patients were categorized as poor (70), intermediate (159), and fast (21) metabolizers. The rs1057910 AC genotype was associated with lower post-induction MBP. This association remained significant after adjustment for baseline MBP, rs1799853 genotype, age, BMI, and sex at 3, 5, and 10 min. No comparable consistent association was observed for rs1799853. Because no minor-allele homozygotes were detected, analyses were restricted to the genotype groups observed in the cohort. The HR decline was not significantly related to the presence of wild-type alleles of either SNP. This study highlights the clinical significance of two commonly occurring variants of CYP2C9 in predicting propofol metabolism and hemodynamic variability. The findings emphasize the potential of pharmacogenetic profiling to guide personalized propofol dosing.