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- Title
PXR haplotype clusters will affect the pharmacokinetics of ciclosporin in Chinese renal transplant recipients.
- Authors
Li, Danying; Zhu, Huaijun; Luo, Xuemei; Ge, Weihong
- Abstract
Objective: PXR was reported to be the key nuclear receptor regulating the expression of metabolizing enzymes and transporters. The aim of this study was to evaluate the influence of PXR haplotype clusters on ciclosporin concentration in Chinese renal transplant recipients during the early stage after transplantation. Methods: A total of 98 recipients receiving ciclosporin were genotyped by PCR‐RFLP, and the ciclosporin concentration was determined by EMIT. Key findings: The frequency of IVS2 55A>G, IVS2 78A>G, IVS6‐17C>T, 1792A>G, 1944T>C and 2654T>C variant alleles was 0.343, 0.332, 0.378, 0.515, 0.520 and 0.393, which fitted Hardy–Weinberg equilibrium. Only the IVS6‐17C>T and 2654T>C were significantly associated with the ciclosporin C2/D during the end of the first month. The mean ciclosporin C2/D level of the PXR*1B haplotype clusters was 1.3‐fold and 1.2‐fold higher compared with the *1A and *1C. No significant difference was observed in CsA C2/D between the PXR*1A and PXR*1C. We found no difference in C0/D among the six genotypes or the three haplotype clusters. Conclusions: The PXR*1B in Chinese renal transplant patients was associated with ciclosporin concentration. Genetic polymorphisms and specific haplotype clusters in PXR could have significant contributory roles in affecting interethnic variations in drug disposition in the Chinese population.
- Subjects
KIDNEY transplantation; NUCLEAR receptors (Biochemistry); HAPLOTYPES; PREGNANE X receptor; PHARMACOKINETICS; GENETIC polymorphisms
- Publication
Journal of Pharmacy & Pharmacology, 2020, Vol 72, Issue 2, p271
- ISSN
0022-3573
- Publication type
Academic Journal
- DOI
10.1111/jphp.13206