title: Patients with CYP3A4*1G genetic polymorphism consumed significantly lower amount of sufentanil in general anesthesia during lung resection.
abstract: CYP3A4, an isoform of cytochrome P450 enzymes, is responsible for the metabolism of 45% to 60% of currently prescribed drugs. It has been shown that CYP3A4*1G, a single nucleotide polymorphism (SNP), affects the enzymatic activity of CYP3A4. Sufentanil, a synthetic opioid commonly used for the induction and maintenance of general anesthesia, analgesia, and sedation, is mainly metabolized by CYP3A4. So far, the impact of CYP3A4*1G on sufentanil metabolism has not been investigated. In the present study, we first determined the frequency of CYP3A4*1G polymorphism in patients of Chinese Han nationality who underwent lung resection, and then compared the amount of sufentanil used in general anesthesia during the surgical procedure between wild type and mutant patients.DNA sequencing was performed to genotype the CYP3A4*1G allele in 191 patients. The sufentanil dosages consumed in general anesthesia were recorded and compared between wild-type and mutant patients.The frequency of the CYP3A4*1G variant allele was 0.202 (77/382). No significant difference was observed in age, body weight, or operation time between wild-type and mutant patients. The amount of sufentanil consumed by patients with the point mutation was significantly lower than that in the wild type group. No significant difference in sufentanil dosages was observed between females and males within wild type or within mutant group.High frequency of CYP3A4*1G variants was detected in patients of Chinese Han nationality. Significantly lower amount of sufentanil was consumed in mutant patients compared with wild type subjects, likely a result of impaired CYP3A4 activity due to the point mutation. These findings suggest genotyping of CYP3A4 might be of value in providing guidance for the use of sufentanil.
authors.affiliation: Department of Anesthesia, Weihai Municipal Hospital, Weihai, Shandong, China.
authors.forename: Huidong
authors.initials: H
authors.lastname: Zhang
authors.forename: Minghao
authors.initials: M
authors.lastname: Chen
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.forename: Songyang
authors.initials: S
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D018686:Anesthetics, Intravenous / Q000008:administration & dosage*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D006801:Humans; D008168:Lung / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017409:Sufentanil / Q000008:administration & dosage*
chemical_list: D018686:Anesthetics, Intravenous; D017409:Sufentanil; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human