Journal Information
Vol. 33. Issue 6.
Pages 324-329 (January 2009)
Vol. 33. Issue 6.
Pages 324-329 (January 2009)
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Pharmacogenetic analysis of the absorption kinetics of cyclosporine in a population of Spanish cardiac transplant patients
Análisis farmacogenético de la cinética de absorción de ciclosporina en una población española de pacientes trasplantados cardíacos
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B. Isla Tejeraa,
Corresponding author
beatrizislatj@gmail.com

Corresponding author.
, M.D. Aumente Rubioa, J. Martínez-Morenob, M. Reyes Maliaa, J.M. Arizónc, A. Suárez Garcíad
a Servicio de Farmacia Hospitalaria, Hospital Universitario Reina Sofía, Córdoba, Spain
b Unidad de Investigación-Fundación Investigación Biomédica de Córdoba (FIBICO), Córdoba, Spain
c Servicio de Cardiología, Hospital Universitario Reina Sofía, Córdoba, Spain
d Departamento de Bioquímica, Facultad de Farmacia, Universidad de Granada, Granada, Spain
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Abstract
Objective

To determine how single nucleotide polymorphisms located on genes MDR1, CYP3A4, and CYP3A5 affect the absorption kinetics of cyclosporine in cardiac transplant patients.

Method

We selected a sample of 30 adult patients having previously undergone a primary cardiac transplant and who had received cyclosporine as an immunosuppressant. During the first month after the transplant, we performed a pharmacokinetic study of each patient to determine values in the cyclosporine concentration area under the 12-hour curve, steady-state cyclosporine concentration, maximum cyclosporine concentration, and time to reach that concentration. Single nucleotide polymorphisms were genotyped in all patients MDR1 3435C > T, CYP3A4-390A > G, and CYP3A5 6986A > G.

Results

Being a carrier of the T-allele for polymorphism MDR1 3435C > T is associated with higher values in the cyclosporine concentration area under the 12-hour curve (P=.01) and in steady-state cyclosporine concentration (P=.05), compared with those from patients who do not carry that allele.

Discussion

Our results show that genotype differences in MDR1 3435C > T can explain part of the variability in cyclosporine absorption among individuals in the population of Spanish cardiac transplant recipients.

Keywords:
Pharmacogenetics
Cardiac transplant
Cyclosporine
Pharmacokinetics
Resumen
Objetivo

Determinar el papel de polimorfismos de nucleótido único localizados en los genes MDR1, CYP3A4 y CYP3A5 sobre la cinética de absorción de ciclosporina en pacientes trasplantados cardíacos.

Método

Se seleccionó una muestra de 30 pacientes adultos sometidos a un primer trasplante de corazón que habían recibido ciclosporina como tratamiento inmunosupresor. En el primer mes después del trasplante se realizó un estudio farmacocinético a cada paciente para determinar los valores del área de concentración de ciclosporina bajo la curva de 12 h, concentración de ciclosporina en estado de equilibrio, concentración de ciclosporina máxima y el tiempo en alcanzar dicha concentración. En todos los pacientes se genotipificaron los polimorfismos de nucleótido único MDR1 3435C > T, CYP3A4-390A > G y CYP3A5 6986A > G.

Resultados

Ser portador del alelo T para el polimorfismo MDR1 3435C > T se asoció a valores mayores de área de concentración de ciclosporina bajo la curva de 12 h (p = 0,01) y de concentración de ciclosporina en estado de equilibrio (p = 0,05), en comparación con los pacientes no portadores de dicho alelo.

Discusión

Nuestros resultados muestran que las diferencias genotípicas de MDR1 3435C > T podrían explicar parte de la variabilidad interindividual en la absorción de la ciclosporina en la población española de trasplantados cardíacos.

Palabras clave:
Farmacogenética
Trasplante cardíaco
Ciclosporina
Farmacocinética
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