Population pharmacokinetic study of cyclosporine in the hematopoietic stem cell transplant recipients.
Int J Clin Pharmacol Ther
; 51(7): 568-75, 2013 Jul.
Article
en En
| MEDLINE
| ID: mdl-23611568
ABSTRACT
OBJECTIVES:
The aim of this study is to investigate the population pharmacokinetics (PopPK) of cyclosporine (CsA) in the Chinese hematopoietic stem cell transplantation (HSCT) recipients for promoting the individualization of CsA administration.METHODS:
A total of 887 retrospective drug monitoring data points were collected from 58 HSCT recipients. Whole blood samples were collected at predose (C0) and 2 hours (C2) post dose. The administration of CsA was intermittent intravenous infusion, continuous intravenous infusion and oral. Population modeling was performed using the NONMEM (nonlinear mixedeffect modeling) program. A one compartment pharmacokinetic model was used to fit the data.RESULTS:
Body surface area (BSA), administration route and postoperative days were identified as significant covariates for clearance (CL) according to the final model CL = 31.0 × (BSA/1.59)0.761 × (ROUT) × (POD), where ROUT was 1.91 if the administration route was intravenous infusion, otherwise it is equal to 1. The POD was 0.818, 0.753, 0.539, and 0.509 for posttransplant Days 0 - 10, 11 - 20, 21 - 30 and more than 30 days, respectively. Administration route was a significant covariate for volume (V) according to the final model V = 192 × (ROUT), where ROUT was 4.10, 3.63 and 1 when the administration route was continuous intravenous infusion, intermittent intravenous infusion and oral. The other covariates were not identified as a significant effect on CsA pharmacokinetic parameters.CONCLUSION:
Body surface area, administration route and postoperative days should be considered in individual pharmacotherapy of cyclosporine for HSCT patient to achieve the desired therapeutic target.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ciclosporina
/
Trasplante de Células Madre Hematopoyéticas
/
Inmunosupresores
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Humans
/
Middle aged
País/Región como asunto:
Asia
Idioma:
En
Revista:
Int J Clin Pharmacol Ther
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2013
Tipo del documento:
Article
País de afiliación:
China