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Dynamic effects of CYP 3A5 polymorphism on dose requirement and trough concentration of tacrolimus in renal transplant recipients
Author(s) -
Chen P.,
Li J.,
Li J.,
Deng R.,
Fu Q.,
Chen J.,
Huang M.,
Chen X.,
Wang C.
Publication year - 2017
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.12480
Subject(s) - tacrolimus , renal transplant , cyp3a5 , medicine , trough (economics) , pharmacology , urology , kidney transplant , kidney transplantation , transplantation , biology , genotype , genetics , gene , macroeconomics , economics
Summary What is known and objective Tacrolimus is a widely used immunosuppressive drug with marked pharmacokinetic variability partly due to CYP 3A5 polymorphism. Our study aimed to investigate the dynamic effects of CYP 3A5 genotypes on dose requirement and trough concentration ( C 0 ) of tacrolimus in renal transplant recipients. Methods A total of 194 Chinese renal transplant recipients received oral tacrolimus twice daily. Whole‐blood C 0 of tacrolimus were measured on the 3rd day, 7th day, 14th day, 1st month, 3rd month and 6th month post‐transplantation. CYP 3A5 genotypes were determined and the recipients were categorized as CYP 3A5 expressers ( CYP 3A5 *1 allele carriers) and non‐expressers (homozygous CYP 3A5 *3). The correlated serum creatinine, haematocrit and albumin were also detected. Results The allele frequencies for CYP 3A5 *1/*1, *1/*3 and *3/*3 were 7·7%, 44·8% and 47·4%, respectively. There were no significant variability in serum creatinine, haematocrit and albumin values between CYP 3A5 expressers and non‐expressers. Larger doses were administered to CYP 3A5 expressers than to non‐expressers after surgery except the initial dose. C 0 were much lower in CYP 3A5 expressers than in non‐expressers on the 3rd day, 7th day, 14th day and 1st month post‐transplantation ( P < 0·01); however, no significant differences were found on the 3rd and 6th months post‐transplantation. All of the dose‐adjusted C 0 in CYP 3A5 expressers were significantly lower than non‐expressers ( P < 0·01). Less of the recipients achieving target C 0 (4–8 ng/mL) were found in CYP 3A5 expressers than in non‐expressers after initial dose (35·7% vs. 50%). Meanwhile, CYP 3A5 non‐expressers were detected having higher C 0 (>8 ng/mL) during 3 months post‐transplantation. Besides, the proportions in the two groups both increased gradually over time and up to 91·8% and 94% on the 6th month, respectively. What is new and conclusion There are no significant differences in serum creatinine, haematocrit and albumin values between CYP 3A5 expressers and non‐expressers. CYP 3A5 expressers have decreased dose‐adjusted tacrolimus C 0 when compared to non‐expressers. Dose‐adjusted C 0 of tacrolimus increases in a time‐dependent manner in both groups.