CYP2C19 genotype affects diazepam pharmacokinetics and emergence from general anesthesia

Objectives Diazepam is widely used to relieve preoperative anxiety in patients. The objective of this study was to investigate the effects of polymorphism in CYP2C19 and the effects of CYP3A4 messenger ribonucleic acid (mRNA) content in blood on recovery from general anesthesia and on diazepam pharmacokinetics. Methods Sixty‐three Japanese patients were classified into the following 3 genotype (phenotype) groups on the basis of polymerase chain reaction–restriction fragment length polymorphism analysis of CYP2C19 polymorphism: no variants, *1/*1 (extensive metabolizer [EM]); 1 variant, *1/*2 or *1/*3 (intermediate metabolizer [IM]); and 2 variants, *2/*2, *2/*3, or *3/*3 (poor metabolizer [PM]). We assessed the effects of these polymorphisms and of CYP3A4 mRNA content in the lymphocytes on the patients' recovery from general anesthesia. Results CYP2C19 genotyping analysis in the 63 subjects showed that 32%, 46%, and 22% of subjects were classified into the EM, IM, and PM groups, respectively. The PM subjects showed a larger area under the curve representing the concentration of diazepam over a 24‐hour period (AUC0–24) (2088 ± 378 ng/mL · h−1, P = .0259), lower clearance of diazepam (0.049 ± 0.009 L · h−1 · kg−1, P = .0287), and longer emergence time (median, 18 minutes; 25th‐75th percentile range, 13–21 minutes; P