title: Value of CYP3A5 genotyping on determining initial dosages of tacrolimus for Chinese renal transplant recipients.
abstract: Optimal blood levels of tacrolimus in transplant recipients are critically important to preserve the allograft. Suboptimal doses of the immunosuppressant can result in allograft toxicity or rejection. In the present study, we determined CYP3A5 genotypes of patients and analyzed their medical documents in 2 successive periods. In the first period, a fixed initial dosage of 0.1 mg/kg was prescribed daily for 28 patients regardless of their CYP3A5 genotype. In the second period, CYP3A5 genotyping was performed with polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. The frequency distribution of CYP3A5 genotypes was 47.4% (38/78) for *1/*3, 2.6% (2/78) for *1/*1, and 50% (39/78) for *3/*3. The patients with *1/*3 had shown significantly lower tacrolimus blood levels than those with the *3/*3 when the initial dose of 0.10 mg/kg was given for 2 weeks postoperatively. In the second period, initial dosages were selected according to individuals' CYP3A5 genotypes, 0.08 mg/kg/d for recipients with CYP3A5 *3/*3 and 0.15 mg/kg/d for recipients with *1/*3. Adjustment of the initial dosage of tacrolimus was documented to improve the proportion of patients achieving target drug blood levels in the early postoperative stage: from 46.7% to 81.8% of the *1/*3 group and from 46.2% to 73.1% of the *3/*3 group on the third day. In conclusion, CYP3A5 polymorphism plays an important role in influencing tacrolimus blood levels. Initial tacrolimus dosage selection based on CYP3A5 genotyping can improve drug blood levels in the early stage following renal transplantation.
authors.affiliation: Department of Urology, Beijing Chaoyang Hospital, Institute of Urology, China Capital Medical University, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: W
authors.initials: W
authors.lastname: Tong
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D016009:Chi-Square Distribution; D002681:China; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D054796:Drug Dosage Calculations; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D016030:Kidney Transplantation / Q000208:ethnology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D013256:Steroids / Q000008:administration & dosage; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D013256:Steroids; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D009173:Mycophenolic Acid; D016559:Tacrolimus