Effects of CYP3A5 and ABCB1 Genetics Variant on Tacrolimus Pharmacokinetics in Algerian adult Kidney Transplant Patients

Boudia, F.

doi:10.18535/jmscr/v4i4.34

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“…In a previous study in 173 post-renal transplant patients, CYP3A5 expressors exhibited a higher apparent oral tacrolimus clearance than CYP3A5 non-expressors [ 14 ]. However, Boudia et al [ 15 ] reported that the CYP3A5 polymorphisms did not influence tacrolimus pharmaco kinetics in an Algerian population (n=62). Further, tacrolimus clearance was not related to the CYP3A5 genotype in stable renal transplant recipients (n=118) [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of cytochrome P450 3A5 polymorphism on the pharmacokinetics of tacrolimus in renal transplant recipients

Htun

Than

Swe

2020

Korean J Transplant

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Background Renal transplant is an effective treatment option for end-stage kidney disease and tacrolimus is one of the most commonly used immunosuppressant drugs in renal transplant patients. Tacrolimus is a substrate of cytochrome P450 3A5 (CYP3A5), and a narrow therapeutic index and large inter-individual variability. The objective of this study was to determine the frequency of CYP3A5*3 polymorphism and its effect on the pharmacokinetics of tacrolimus in post-renal transplant patients at Mandalay General Hospital. Methods Three different genotypes of CYP3A5 were determined by polymerase chain reaction-restriction fragment length polymorphism in 54 post-renal transplant recipients. Tacrolimus trough concentrations (C trough ) were measured by enzyme multiplied immunoassay technique following method validation. The apparent clearance (CL/F) was calculated from measured C trough . Results The frequency of CYP3A5*1 allele was 0.24 and that of CYP3A5*3 allele was 0.76 in the study sample. There were a total of 33 CYP3A5 non-expressors (patients with CYP3A5*3/*3 genotype) and 21 CYP3A5 expressors (patients with CYP3A5*1/*1 or CYP3A5*1/*3 genotype), respectively. CL/F was significantly lower in the non-expressor group than in the expressor group (mean±standard deviation, 12.53±5.28 vs. 21.22±5.95 L/hr; P<0.001). The mean C trough and concentration dose ratio (C/D) for tacrolimus in CYP3A5 non-expressors were significantly higher than those in CYP3A5 expressors (C trough , 7.14±2.56 vs. 5.92±1.76 ng/mL; C/D, 6.92±4.11 vs. 2.89±1.85 ng/mL/mg), respectively (P<0.05). Conclusions In this study, 76% of the Myanmar renal transplant recipients carried the CYP3A5*3 allele that was associated with lower functional activity of the CYP3A5 enzyme a lower CL/F of tacrolimus in these Thus, CYP3A5 polymorphism influences the pharmacokinetics of tacrolimus, which may affect the pharmacological response to tacrolimus

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Section: Introductionmentioning

confidence: 99%