title: Benefits of minimizing immunosuppressive dosage according to cytochrome P450 3A5 genotype in liver transplant patients: findings from a single-center study.
abstract: We evaluated the clinical efficacy of tailoring tacrolimus dosage to cytochrome P450 (CYP) 3A5 genotype in liver transplant patients. One hundred patients who received tacrolimus-based therapy were included in the retrospective study in which the relationship between the tacrolimus blood trough concentration/dosage ratio and the CYP3A5 genotype of both donors and recipients was determined. Subsequently, 106 patients were continuously enrolled in a prospective study and followed-up for 6 months; the relationship between tacrolimus dosage and CYP3A5 genotype was also determined. Rates of acute rejection, hepatotoxicity, renal toxicity, neurotoxicity, hypertension, and hyperglycemia were compared between the groups. During the 6 months following liver transplantation, the mean tacrolimus concentration/dosage ratio among patients who did not have the CYP3A5*1 genotype and who received a transplant from a donor with the same genotype (24/100, 24% of patients) was higher than that among patients who did have the CYP3A5*1 genotype and/or had a donor with the same genotype (76/100, 76% of patients). In the second part of the study, the tacrolimus dosage was tailored to CYP3A5 genotype and 24 patients (22.64%) received a lower dose. There was an obvious decrease in acute rejection, hepatotoxicity, renal toxicity, neurotoxicity, hypertension, hyperglycemia, and Pneumocystis carinii infection among the latter group. A lower tacrolimus dose was suitable for about 25% of the liver transplant patients, as these patients did not have the CYP3A5*1 genotype and received a transplant from a donor with the same genotype. Tailoring the tacrolimus dosage according to the CYP3A5 genotype could reduce rejection and adverse effects.
authors.affiliation: Liver Transplant Center, Beijing You An Hospital, Capital Medical University, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: President's Office, Beijing You An Hospital, Capital Medical University, Beijing, China.
authors.forename: N
authors.initials: N
authors.lastname: Li
authors.affiliation: Pharmacology Base, Beijing You An Hospital, Capital Medical University, Beijing, China.
authors.forename: M X
authors.initials: MX
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, General Hospital of PLA, Beijing, China lushichun201449@163.com.
authors.forename: S C
authors.initials: SC
authors.lastname: Lu
mesh_terms: D000328:Adult; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006084:Graft Rejection / Q000209:etiology; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology; D006973:Hypertension / Q000209:etiology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D007674:Kidney Diseases / Q000209:etiology; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D013997:Time Factors; D014019:Tissue Donors
chemical_list: D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus