Effect of the Interrelation between CYP3A5 Genotype, Concentration/Dose Ratio and Intrapatient Variability of Tacrolimus on Kidney Graft Function: Monte Carlo Simulation Approach

Background: Tacrolimus (Tac) is characterized by large between- and within-patient (IPV) variability in pharmacokinetics and exposure. Aim: This study aimed to assess and validate the effect of Tac IPV and trough concentration-to-dose ratio (C0</su...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Nikola Stefanović, Radmila Veličković-Radovanović, Katarina Danković, Ivan Pavlović, Aleksandra Catić-Đorđević, Jelena Bašić, Milena Despotović, Tatjana Jevtović-Stoimenov, Branka Mitić, Tatjana Cvetković
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	intrapatient variability kidney transplantation CYP3A5 genotype tacrolimus therapeutic drug monitoring Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/f516b028f4de4006b5ad0a0a02ba1e0b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f516b028f4de4006b5ad0a0a02ba1e0b
record_format	dspace
spelling	oai:doaj.org-article:f516b028f4de4006b5ad0a0a02ba1e0b2021-11-25T18:42:32ZEffect of the Interrelation between CYP3A5 Genotype, Concentration/Dose Ratio and Intrapatient Variability of Tacrolimus on Kidney Graft Function: Monte Carlo Simulation Approach10.3390/pharmaceutics131119701999-4923https://doaj.org/article/f516b028f4de4006b5ad0a0a02ba1e0b2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1970https://doaj.org/toc/1999-4923<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.Nikola StefanovićRadmila Veličković-RadovanovićKatarina DankovićIvan PavlovićAleksandra Catić-ĐorđevićJelena BašićMilena DespotovićTatjana Jevtović-StoimenovBranka MitićTatjana CvetkovićMDPI AGarticleintrapatient variabilitykidney transplantationCYP3A5 genotypetacrolimustherapeutic drug monitoringPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1970, p 1970 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	intrapatient variability kidney transplantation CYP3A5 genotype tacrolimus therapeutic drug monitoring Pharmacy and materia medica RS1-441
spellingShingle	intrapatient variability kidney transplantation CYP3A5 genotype tacrolimus therapeutic drug monitoring Pharmacy and materia medica RS1-441 Nikola Stefanović Radmila Veličković-Radovanović Katarina Danković Ivan Pavlović Aleksandra Catić-Đorđević Jelena Bašić Milena Despotović Tatjana Jevtović-Stoimenov Branka Mitić Tatjana Cvetković Effect of the Interrelation between CYP3A5 Genotype, Concentration/Dose Ratio and Intrapatient Variability of Tacrolimus on Kidney Graft Function: Monte Carlo Simulation Approach
description	<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.
format	article
author	Nikola Stefanović Radmila Veličković-Radovanović Katarina Danković Ivan Pavlović Aleksandra Catić-Đorđević Jelena Bašić Milena Despotović Tatjana Jevtović-Stoimenov Branka Mitić Tatjana Cvetković
author_facet	Nikola Stefanović Radmila Veličković-Radovanović Katarina Danković Ivan Pavlović Aleksandra Catić-Đorđević Jelena Bašić Milena Despotović Tatjana Jevtović-Stoimenov Branka Mitić Tatjana Cvetković
author_sort	Nikola Stefanović
title	Effect of the Interrelation between CYP3A5 Genotype, Concentration/Dose Ratio and Intrapatient Variability of Tacrolimus on Kidney Graft Function: Monte Carlo Simulation Approach
title_short	Effect of the Interrelation between CYP3A5 Genotype, Concentration/Dose Ratio and Intrapatient Variability of Tacrolimus on Kidney Graft Function: Monte Carlo Simulation Approach
title_full	Effect of the Interrelation between CYP3A5 Genotype, Concentration/Dose Ratio and Intrapatient Variability of Tacrolimus on Kidney Graft Function: Monte Carlo Simulation Approach
title_fullStr	Effect of the Interrelation between CYP3A5 Genotype, Concentration/Dose Ratio and Intrapatient Variability of Tacrolimus on Kidney Graft Function: Monte Carlo Simulation Approach
title_full_unstemmed	Effect of the Interrelation between CYP3A5 Genotype, Concentration/Dose Ratio and Intrapatient Variability of Tacrolimus on Kidney Graft Function: Monte Carlo Simulation Approach
title_sort	effect of the interrelation between cyp3a5 genotype, concentration/dose ratio and intrapatient variability of tacrolimus on kidney graft function: monte carlo simulation approach
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f516b028f4de4006b5ad0a0a02ba1e0b
work_keys_str_mv	AT nikolastefanovic effectoftheinterrelationbetweencyp3a5genotypeconcentrationdoseratioandintrapatientvariabilityoftacrolimusonkidneygraftfunctionmontecarlosimulationapproach AT radmilavelickovicradovanovic effectoftheinterrelationbetweencyp3a5genotypeconcentrationdoseratioandintrapatientvariabilityoftacrolimusonkidneygraftfunctionmontecarlosimulationapproach AT katarinadankovic effectoftheinterrelationbetweencyp3a5genotypeconcentrationdoseratioandintrapatientvariabilityoftacrolimusonkidneygraftfunctionmontecarlosimulationapproach AT ivanpavlovic effectoftheinterrelationbetweencyp3a5genotypeconcentrationdoseratioandintrapatientvariabilityoftacrolimusonkidneygraftfunctionmontecarlosimulationapproach AT aleksandracaticđorđevic effectoftheinterrelationbetweencyp3a5genotypeconcentrationdoseratioandintrapatientvariabilityoftacrolimusonkidneygraftfunctionmontecarlosimulationapproach AT jelenabasic effectoftheinterrelationbetweencyp3a5genotypeconcentrationdoseratioandintrapatientvariabilityoftacrolimusonkidneygraftfunctionmontecarlosimulationapproach AT milenadespotovic effectoftheinterrelationbetweencyp3a5genotypeconcentrationdoseratioandintrapatientvariabilityoftacrolimusonkidneygraftfunctionmontecarlosimulationapproach AT tatjanajevtovicstoimenov effectoftheinterrelationbetweencyp3a5genotypeconcentrationdoseratioandintrapatientvariabilityoftacrolimusonkidneygraftfunctionmontecarlosimulationapproach AT brankamitic effectoftheinterrelationbetweencyp3a5genotypeconcentrationdoseratioandintrapatientvariabilityoftacrolimusonkidneygraftfunctionmontecarlosimulationapproach AT tatjanacvetkovic effectoftheinterrelationbetweencyp3a5genotypeconcentrationdoseratioandintrapatientvariabilityoftacrolimusonkidneygraftfunctionmontecarlosimulationapproach
_version_	1718410809562890240

Effect of the Interrelation between CYP3A5 Genotype, Concentration/Dose Ratio and Intrapatient Variability of Tacrolimus on Kidney Graft Function: Monte Carlo Simulation Approach

Ejemplares similares