Effect of the Interrelation between CYP3A5 Genotype, Concentration/Dose Ratio and Intrapatient Variability of Tacrolimus on Kidney Graft Function: Monte Carlo Simulation Approach
<b>Background</b>: Tacrolimus (Tac) is characterized by large between- and within-patient (IPV) variability in pharmacokinetics and exposure. <b>Aim</b>: This study aimed to assess and validate the effect of Tac IPV and trough concentration-to-dose ratio (C<sub>0</su...
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| Autores principales: | , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/f516b028f4de4006b5ad0a0a02ba1e0b |
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| Sumario: | <b>Background</b>: Tacrolimus (Tac) is characterized by large between- and within-patient (IPV) variability in pharmacokinetics and exposure. <b>Aim</b>: This study aimed to assess and validate the effect of Tac IPV and trough concentration-to-dose ratio (C<sub>0</sub>/D) over 6–12 months on reduced estimated glomerular filtration rate (eGFR) values in the late period after kidney transplantation (Tx), applying Monte Carlo (MC) simulation. <b>Methods</b>: The previously published linear regression was the basis for MC simulation, performed to determine how variations in significant predictors affect the distribution of eGFR from 13 to 36 months post-transplantation. The input C<sub>0</sub>/D values were derived from CYP3A5 genotype subgroups. <b>Results</b>: Patients characterized by high Tac IPV and low mean C<sub>0</sub>/D over 6–12 months could have been at greater risk of lower eGFR values in a three-year period following Tx compared to the other patient groups. This effect was more pronounced in patients with a lower eGFR at the 6th month and a history of acute rejection. The proven contribution of CYP3A5 expresser genotype to low C<sub>0</sub>/D values may suggest its indirect effect on long-term graft function. <b>Conclusion</b>: The findings indicate that simultaneous assessment of Tac IPV, C<sub>0</sub>/D, and CYP3A5 genotype may identify patients at risk of deterioration of graft function in the long-term post-transplantation period. |
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