Population pharmacokinetics of tacrolimus in Chinese renal transplant patients / 药学学报
Yao Xue Xue Bao
; (12): 695-701, 2008.
Article
in Zh
| WPRIM
| ID: wpr-277810
Responsible library:
WPRO
ABSTRACT
The goal of this study is to investigate the population pharmacokinetics of oral tacrolimus in Chinese renal transplant patients and to identify possible relationship between covariates and population parameters. Details of drug dosage history, sampling time and concentration of 802 data points in 58 patients were collected retrospectively. Before analysis, the 58 patients were randomly allocated to either the model building group (n=41) or the validation group (n=17). Population pharmacokinetic data analysis was performed using the nonlinear mixed-effects model (NONMEM) program on the model building group. The pharmacokinetics of tacrolimus was best described by a one compartment model with first-order absorption and elimination. Typical values of apparent clearance (CL/F), apparent volume of distribution (V/F) were estimated. A number of covariates including demographic index, clinical index and coadministration of other drugs were evaluated statistically for their influence on these parameters. The final population model related clearance with POD (post operative days), HCT (haematocrit), AST (aspartate aminotransferase) and coadministration of nicardipine and diltiazem. Predictive performance of the final model evaluated with the validation group showed insignificant bias between observed and model predicted concentrations. Typical value of CL/F and V/F was 21.7 L x h(-1) and 241 L, inter-patient variability (RSD) in CL/F and V/F was 41.6% and 49.7%, respectively. The residual variability (SD) between observed and model-predicted concentrations was 2.19 microg x L(-1). The population pharmacokinetic model of tacrolimus in Chinese renal transplant patients was established and significant covariates on the tacrolimus model were identified.
Full text:
1
Index:
WPRIM
Main subject:
Blood
/
Pharmacokinetics
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Metabolic Clearance Rate
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Administration, Oral
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Retrospective Studies
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Models, Statistical
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Kidney Transplantation
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Tacrolimus
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Nonlinear Dynamics
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Asian People
Type of study:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limits:
Adolescent
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Adult
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Aged
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Female
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Humans
/
Male
Language:
Zh
Journal:
Yao Xue Xue Bao
Year:
2008
Type:
Article