P-glycoprotein functional activity in «soviet chinchilla» rabbits during pregnancy
- 作者: Popova N.M.1, Shchulkin A.V.1, Chernykh I.V.1, Esenina A.S.1, Gradinar M.M.1, Nikiforova L.V.1, Ryabkov A.N.1, Yakusheva E.N.1
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隶属关系:
- Ryazan State Medical University
- 期: 卷 26, 编号 4 (2018)
- 页面: 466-473
- 栏目: Original study
- URL: https://journals.rcsi.science/pavlovj/article/view/10842
- DOI: https://doi.org/10.23888/PAVLOVJ2018264466-473
- ID: 10842
如何引用文章
详细
P-glycoprotein (Pgp, ABCB1-protein) is a membrane transporter protein that plays the key role in pharmacokinetics of drugs with a broad spectrum of action. Substrates of this transporter are some medical drugs (antibacterial, antiretroviral, hypotensive) that are prescribed to pregnant women for long-term intake, sometimes throughout the whole gestation period.
Aim to study the activity of Pgp on the organism level in rabbits of Soviet Chinchilla breed in pregnancy.
Materials and Methods. The study was performed on 21 Soviet Chinchilla female rabbits (3000-3500 g). The animals were divided into 3 series. The first series (n=6) included rabbits with 7 days of pregnancy; the second series (n=5) − animals with 14 days of pregnancy; the third series (n=10) − rabbits with 21 days of pregnancy. 7 Days before the study and in the indicated gestation periods, functional activity of Pgp was assessed by the pharmacokinetics of marker transporter substrate – fexofenadine, after its single oral introduction (67.5 mg/kg). Besides, serum concentrations of progesterone, estradiol, testosterone and prolactin were determined by radio immune method
Results. In all the studied gestational periods, serum concentrations of estradiol, testosterone and prolactin did not significantly differ from those before pregnancy, but the level of progesterone in blood serum was significantly elevated above the norm. On the 7th day of pregnancy pharmacokinetic parameters of fexofenadine did not show any reliable changes as compared to the initial va-lues. On the 14th day of pregnancy a reliable increase in Cmax, AUC0-t, T1/2 of fexofenadine was noted as compared to the parameters before pregnancy, which indicates a decrease in Pgp functional activity on the organism level. On the 21st day of pregnancy Cmax of fexofenadine remained elevated. Other pharmacokinetic parameters of fexofenadine did not show reliable changes. Conclusion. Reduction in Pgp functional activity, determined by the pharmacokinetics of its marker substrate (fexofenadine), was noted in rabbits of Soviet Chinchilla breed on the 14th and 21st days of pregnancy with the underlying significant increase in progesterone level.
作者简介
Natalia Popova
Ryazan State Medical University
编辑信件的主要联系方式.
Email: p34-66@yandex.ru
ORCID iD: 0000-0002-5166-8372
SPIN 代码: 7553-9852
Researcher ID: B-1130-2016
MD, PhD, Senior Teacher of Pharmacology Department with Course of Pharmacy of Continuing Professional Education Faculty
俄罗斯联邦, 9,Vysokovoltnaja,Ryazan,390026Aleksey Shchulkin
Ryazan State Medical University
Email: vestnik@rzgmu.ru
ORCID iD: 0000-0003-1688-0017
SPIN 代码: 2754-1702
Researcher ID: N-9143-2016
MD, PhD, Assistant Professor of Pharmacology Department with Course of Pharmacy of Continuing Professional Education Faculty
俄罗斯联邦, 9,Vysokovoltnaja,Ryazan,390026Ivan Chernykh
Ryazan State Medical University
Email: vestnik@rzgmu.ru
ORCID iD: 0000-0002-5618-7607
SPIN 代码: 5238-6165
Researcher ID: 1389-2017
PhD in Biological sciences, Assistant of the Department of General Chemistry and Pharmachemistry
俄罗斯联邦, 9,Vysokovoltnaja,Ryazan,390026Anna Esenina
Ryazan State Medical University
Email: vestnik@rzgmu.ru
ORCID iD: 0000-0002-3984-8979
Researcher ID: k-3849-2018
Student
俄罗斯联邦, 9,Vysokovoltnaja,Ryazan,390026Maria Gradinar
Ryazan State Medical University
Email: vestnik@rzgmu.ru
ORCID iD: 0000-0002-2246-4127
Researcher ID: k-3854-2018
Student
俄罗斯联邦, 9,Vysokovoltnaja,Ryazan,390026Larisa Nikiforova
Ryazan State Medical University
Email: vestnik@rzgmu.ru
ORCID iD: 0000-0003-4369-0729
SPIN 代码: 8735-8565
Researcher ID: Х-6868-2018
MD, Senior Researcher of Central Research Laboratory
俄罗斯联邦, 9,Vysokovoltnaja,Ryazan,390026Alexander Ryabkov
Ryazan State Medical University
Email: p34-66@yandex.ru
ORCID iD: 0000-0003-4705-747X
Researcher ID: S-1779-2016
MD, PhD, Assistant Professor of Pharmacology Department with Course of Pharmacy of Continuing Professional Education Faculty
俄罗斯联邦, 9,Vysokovoltnaja,Ryazan,390026Elena Yakusheva
Ryazan State Medical University
Email: p34-66@yandex.ru
ORCID iD: 0000-0001-6887-4888
SPIN 代码: 2865-3080
Researcher ID: T-6343-2017
MD, PhD, Professor, Head of Pharmacology Department with Course of Pharmacy of Conti-nuing Professional Education Faculty
俄罗斯联邦, 9,Vysokovoltnaja,Ryazan,390026参考
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