Population pharmacokinetics of combined ethinylestradiol/gestodene transdermal contraceptive tablets and patches in Chinese healthy volunteers
10.13699/j.cnki.1001-6821.2018.07.039
- VernacularTitle:复方孕二烯酮片剂和贴片在中国健康受试者中的群体药代动力学研究
- Author:
Yang LIU
1
;
Chao ZHANG
;
Suo-Di ZHAI
Author Information
1. 北京大学第三医院药剂科
- Keywords:
gestodene;
ethinylestradiol;
population pharmacokinetics;
transdermal contraceptive patch
- From:
The Chinese Journal of Clinical Pharmacology
2018;34(7):870-874,880
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the population pharmacokinetics (PPK) of combined gestodene (GSD)/ethinylestradiol (EE) oral tablet and transdermal contraceptive patch in Chinese healthy volunteers,and provide theoretic supports for personalized medication.Methods An open-label,two-period comparative study was conducted in 12 healthy women volunteers.A single dose of combined GSD/EE oral tablet and transdermal contraceptive patch were administered.Blood samples at different time points after dose were collected,and concentrations were analyzed.A reliable,highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry assay method was developed in this study to determine the plasma concentrations of GSD and EE.The population pharmacokinetic parameters were estimated by nonlinear mixed effect model (NONMEM).Results A two -compartment model with first-order absorption and first-order elimination process was built as the structural model for GSD and EE of the tablet,respectively.Meanwhile,a one-compartment model with zero-order input and first-order elimination best described the GSD plasma concentrations after a single dose administration of the patch,and a one -compartment model with first-order absorption and first-order elimination for EE of the patch adequately described the data.When covariates were tested,none were found to adequately explain the changes of GSD and EE pharmacokinetic parameters in the PPK model for each route.Conclusion The established PPK models are capable of depicting pharmacokinetics of combined GSD/EE oral tablet and transdermal contraceptive patch in Chinese healthy volunteers.The final models are stable,and further research is warranted to study the effect of the potential covariates on GSD and EE pharmacokinetic parameters to improve the predictive performance.
