Impact of CYP2D6*2A, CYP2D6*4 and CYP3A5*3 genetic polymorphisms on Bisoprolol peak concentration and clinical response in acute coronary syndrome patients.

Abstract

Acute coronary syndrome (ACS) represents a major cause of death. Bisoprolol is commonly used in the management of ACS. This study aims to investigate the impact of CYP2D6*2A, CYP2D6*4 and CYP3A5*3 genetic polymorphisms on pharmacokinetics and clinical response of bisoprolol in ACS patients. This is an open-label cohort study that included 127 ACS patients and studied the effect of CYP3A5*3, CYP2D6*2A and CYP2D6*4 genotyping using real-time polymerase chain reaction on steady state bisoprolol plasma peak concentration analysed by high performance liquid chromatography-fluorescence detector. Regarding CYP3A5*3, the mean peak bisoprolol concentration for CC, CT and TT genotypes were 4.25 ± 1.20, 3.93 ± 1.10 and 1.79 ± 0.69 ng/mL, respectively (P < .001). Higher systolic (126 ± 5.47 mmHg), diastolic blood pressure (82 ± 2.73 mmHg) and heart rate (97.80 ± 3.03 beats/min) were also observed in CYP3A5*3 TT carriers (P < .05). In CYP2D6*2A, the peak concentration of bisoprolol was lower in CC carriers (3.54 ± 1 ng/mL) compared to GG (4.38 ± 1.25 ng/mL) and GC carriers (4.07 ± 1.29 ng/mL, P = .019). In CYP2D6*4, the mean bisoprolol peak concentration in CC carriers was 3.98 ± 1.31 ng/mL, which was lower than T allele carriers (4.5 ± 0.8, P = .02). No differences in heart rate, systolic, diastolic blood pressure or bisoprolol dose were observed among CYP2D6*2A or CYP2D6*4 variants. Smokers exhibited lower bisoprolol peak concentration (3.96 ± 1.2 ng/mL) compared to nonsmokers (4.55 ± 1.34 ng/mL, P = .037). There is an association between CYP3A5*3, CYP2D6*4, CYP2D6*2A variants and bisoprolol peak concentration, which may serve as a guide in the future in choosing the optimum dose of bisoprolol in ACS patients.