Abstract
Aim:
Co-administration of diltiazem can reduce the dosage of cyclosporine (CsA) in patients with renal transplantation. In this study, we investigated how diltiazem altered the relationship between MDR1 genetic polymorphisms and CsA concentration in Chinese patients with renal transplantation.
Methods:
A total of 126 renal transplant patients were enrolled. All the patients received CsA (2–4 mg·kg−1·d−1), and diltiazem (90 mg/d) was co-administered to 76 patients. MDR1-C1236T, G2677T/A, and C3435T polymorphisms were genotyped. The whole blood concentration was measured using the FPIA method, and the adjusted trough concentrations were compared among the groups with different genotypes.
Results:
In all patients, MDR1-C1236T did not influence the adjusted CsA trough concentration. With regard to MDR1-3435, the adjusted CsA trough concentration was significantly higher in TT carriers than in CC and CT carriers when diltiazam was co-administered (58.83±13.95 versus 46.14±7.55 and 45.18±12.35 ng/mL per mg/kg, P=0.011), and the differences were not observed in patients without diltiazam co-administered. With regard to MDR1-2677, the adjusted CsA trough concentration was significantly higher in TT carriers than in GG and GT carriers when diltiazam was co-administered (61.31±12.93 versus 52.25±7.83 and 39.70±7.26 ng/mL per mg/kg, P=0.0001). The differences were also observed in patients without diltiazam co-administered (43.27±5.95 versus 35.22±7.55 and 29.54±5.35 ng/mL per mg/kg, P=0.001). The adjusted CsA trough blood concentration was significantly higher in haplotype T-T-T and haplotype T-T-C carriers than in non-carriers, regardless of diltiazem co-administered.
Conclusion:
MDR1 variants influence the adjusted CsA trough concentration in Chinese patients with renal transplant, and the influence more prominent when diltiazem is co-administered.
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Acknowledgements
This work was supported by the National Major Projects for Science and Technology Development from the Science and Technology Ministry of China (No 2009ZX09304-003), the National Natural Science Foundation of China (No 30572231, 30873124 and 30873125) and the Science and Technology Planning Project of Guangdong Province (No 2007B031511001). We also received financial support from the National Major Projects for Science and Technology Development from Science and Technology Ministry of China (Grant No 2012ZX09506001-004) and the National Natural Science Foundation of China (No 81202600, 81102515, 81072708 and 81173131). The authors would like to thank all doctors, nurses and patients who participated in this study.
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Wang, Yx., Li, Jl., Wang, Xd. et al. Diltiazem augments the influence of MDR1 genotype status on cyclosporine concentration in Chinese patients with renal transplantation. Acta Pharmacol Sin 36, 855–862 (2015). https://doi.org/10.1038/aps.2015.6
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DOI: https://doi.org/10.1038/aps.2015.6
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