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Abstract

Population Pharmacokinetics of Sirolimus in Healthy Chinese Subjects

Author(s): M. Peng, G. Zhao, X. Li and M. Chen*
Department of Pharmacy, the 309th Hospital of PLA, Beijing 100091, Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China

Correspondence Address:
Department of Pharmacy, the 309th Hospital of PLA, Beijing 100091, China, E-mail: lm19851229@126.com


Sirolimus is metabolized by the CYP3A subfamily and is a substrate of the P-glycoprotein. CYP3A5 and MDR1 gene polymorphisms have been reported to influence plasma concentrations of this drug and dose requirements, but some recent studies reported conflicting results. The aim of this study was to develop population pharmacokinetics to identify the potential influencing factors that explain pharmacokinetic variability in healthy Chinese adults. Twenty seven healthy Chinese subjects were enrolled into this study and were genotyped for CYP3A5 (6986A>G), MDR1 (3435C>T). Blood samples at different time point were collected from each subject and blood concentrations were measured. The population pharmacokinetic model was established using the non-linear mixed-effects model method, CYP3A5, MDR1, gender and other factors were evaluated in the model as covariates. The results indicated that CYP3A5 polymorphisms significantly influenced the clearance, the central compartment distribution volume was larger in male than that in female subjects, body surface area showed remarkable impact on peripheral compartment volume. All parameters were estimated with acceptable precision. Visual predictive check and bootstrap indicated that the population model adequately captured the observed profiles. This model may be useful in guiding clinicians to adjust drug dosing regimen.

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Citations : 69022

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