Population pharmacokinetic study of tacrolimus in patients with hematopoietic stem cell transplant / 药学学报
Acta Pharmaceutica Sinica
;
(12): 1145-1151, 2009.
Article
in Chinese
| WPRIM
| ID: wpr-344041
ABSTRACT
The present study is to establish the population pharmacokinetic (PPK) model of tacrolimus and to estimate PPK parameters of tacrolimus for the individualization of tacrolimus administration in patients with hematopoietic stem cell transplant. A total of 671 blood samples were collected from 68 hematopoietic stem cell transplant patients and clinical data were retrospectively collected from the medical records of these patients. Population pharmacokinetical analysis was performed using the nonlinear mixed-effect model (NONMEM) program. The Bootstrap and data splitting were used simultaneously to validate the final population pharmacokinetical models. The basic structural model was best described as one-compartment pharmacokinetical model with first-order absorption and elimination. A number of covariates including demographic characteristic, biochemical and hematological index, combined drugs, inter-occasion variability (IOV) and other variables, e.g. primary disease, post operation days (POD), the type of transplantation and the sources of donor, were screened for their influence on the pharmacokinetic parameters of tacrolimus. The population typical values of tacrolimus CL, V, F were 12.1 L x h(-1), 686 L, 42.2%; and the inter-individual variability of these parameters were 23.5%, 96.4%, 43.8%, respectively. The absorption rate constant was fixed 4.3 h(-1). The residual error between observed and model- predicted concentration was 3.03 ng x mL(-1). The CYP enzyme inhibitor (INHI), POD and age were identified to be the main covariates that influence tacrolimus CL, and hemoglobulin (HGB) was the main covariate that may explain the variability in tacrolimus V. The IOV of CL, V, F were 22.2%, 6.23%, 30.3%, respectively. The population pharmacokinetic data obtained in the present study have significant clinical value for the individualization of tacrolimus therapy in hematopoietic stem cell transplant patients.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Blood
/
Pharmacokinetics
/
Metabolic Clearance Rate
/
Retrospective Studies
/
Tacrolimus
/
Nonlinear Dynamics
/
Hematopoietic Stem Cell Transplantation
/
Immunosuppressive Agents
/
Models, Biological
Type of study:
Observational study
/
Prognostic study
Limits:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
Language:
Chinese
Journal:
Acta Pharmaceutica Sinica
Year:
2009
Type:
Article
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