Robles-Piedras A. L, Romano-Moreno S, Fuentes-Noriega I, Mancilla-Urrea E, Castro-Torres N. N, Dominguez-Ramirez A. M.Population Pharmacokinetic Analysis of Tacrolimus in Adult Mexican Patients with Renal Transplant. Biomed. Pharmacol. J.;8(1)

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Ana Luisa Robles-Piedras^1,2, Silvia Romano-Moreno³, Ines Fuentes-Noriega⁴, Eduardo Mancilla-Urrea⁵, Nelly Norma Castro-Torres⁶ and Adriana Miriam Dominguez-Ramirez.

1Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana. Unidad Xochimilco. Calzada del Hueso 1100, Col. Villa Quietud. Delegación Coyoacán. México, D.F.c.p. 04960. 2Universidad Autónoma del Estado de Hidalgo, Instituto de Ciencias de la Salud, Área Académica de Farmacia. Circuito Ex-Hacienda La Concepción, Km. 1.5. San Agustín Tlaxiaca, Hidalgo.México. c.p. 42160. 3Universidad Autónoma de San Luis Potosí, Facultad de Ciencias Químicas, Laboratorio de Biofarmacia y Farmacocinética. Avenida Dr. Manuel Nava no. 6, Zona Universitaria. San Luis Potosí, SLP.México. c.p. 78240. 4 Universidad Nacional Autónoma de México, Facultad de Química, Departamento de Farmacia, Conjunto “E”, Laboratorio 113. Paseo de la Investigación Científica s/n. Ciudad Universitaria. Delegación Coyoacán. México, D.F.c.p. 04510. 5 Instituto Nacional de Cardiología “Ignacio Chávez”. Departamento de Nefrología. Juan Badiano no. 1, Col. Secc. XVI. Delegación Tlalpan. México, D.F. c.p. 14080. 6 Instituto Nacional de Neurología y Neurocirugía. Laboratorio de Neuropsicofarmacología. Av. Insurgentes Sur 3877, Col. La Fama. Delegación Tlalpan. México, D.F. c.p.14269. 7 Universidad Autónoma Metropolitana. Unidad Xochimilco, Departamento de Sistemas Biológicos, Laboratorio de Farmacocinética. Calzada del Hueso 1100, Col. Villa Quietud. Delegación Coyoacán. México, D.F.c.p. 04960.

DOI : https://dx.doi.org/10.13005/bpj/581

Abstract

The aim of this study was to estimate the population pharmacokinetic parameters of Tacrolimus in Mexican adults undergoing kidney transplantation and to identify the clinical factors affecting Tacrolimus pharmacokinetics. Using Non-linear mixed effects modeling (NONMEM) with First-order absorption and elimination, a total of 592 retrospective-prospective drug monitoring data points were collected from 36 patients with renal transplant receiving Tacrolimus (Prograf® twice daily during the first 6 post-transplantation months and a generic product thereafter. The absorption rate constant was fixed at 4.5 h–1, and the following population pharmacokinetic estimates were obtained: Tacrolimus clearance (CL/F), 22.5 L/h, and apparent volume of distribution (V/F), 812 L. Interindividual variability was 52.9 and 82.1% for CL/F and V/F, respectively. The covariates that significantly affect Tacrolimus pharmacokinetics parameters were concomitantly administered calcium channel blocker drug and hematocrit level. The population pharmacokinetic analysis identified important sources of variability in Tacrolimus pharmacokinetics. The model will help to calculate Tacrolimus dose requirements in Mexican renal transplant recipients according to specific clinical factors affecting Tacrolimus clearance and volume of distribution and it will also be useful for therapeutic drug monitoring.

Keywords

Tacrolimus pharmacokinetics; Mexican; renal transplant