Pharmacokinetics of sildenafil and its metabolite, N-desmethylsildenafil, in rats with liver cirrhosis and diabetes mellitus, alone and in combination

C. Y. Ahn; S. K. Bae; S. H. Bae; H. E. Kang; S. H. Kim; M. G. Lee; W. G. Shin

doi:10.3109/00498254.2010.532885

Pharmacokinetics of sildenafil and its metabolite, N-desmethylsildenafil, in rats with liver cirrhosis and diabetes mellitus, alone and in combination

C. Y. Ahn
, S. K. Bae
, S. H. Bae
, H. E. Kang
, S. H. Kim
, M. G. Lee
, W. G. Shin

Pharmacy

Seoul National University
National Institute of Food and Drug Safety Evaluation
The Catholic University of Korea
Gangneung-Wonju National University

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Pharmacokinetics of sildenafil and its metabolite, N-desmethylsildenafil, in humans and rats with liver cirrhosis (LC) and diabetes mellitus (DM), alone and in combination (LCD) did not seem to be reported. Sildenafil was administered intravenously (10mg/kg) and orally (20mg/kg) to control, LC, DM, and LCD rats. Expression of intestinal CYP isozymes in those rats was also measured. In LC, DM, and LCD rats, the areas under the curve (AUCs) of intravenous sildenafil were significantly greater (by 195%, 54.2%, and 127%, respectively) than controls. In LC and LCD rats, AUCs of oral sildenafil were significantly greater (3010% and 2030%, respectively) than controls. In LC, DM, and LCD rats, significantly greater AUCs of intravenous sildenafil were due to the slower hepatic extraction of sildenafil (because of decrease in the protein expression of hepatic CYP2C11 and 3A subfamily in LC and LCD rats, and CYP2C11 in DM rats). In LC and LCD rats, greater magnitude of increase in AUCs of oral sildenafil than those after the intravenous administration could be mainly due to the decrease in the intestinal extraction of sildenafil (because of decrease in the protein expression of intestinal CYP2C11 in LC and LCD rats).

Original language	English
Pages (from-to)	164-174
Number of pages	11
Journal	Xenobiotica
Volume	41
Issue number	2
DOIs	https://doi.org/10.3109/00498254.2010.532885
State	Published - Feb 2011

Bibliographical note

Funding Information:
This study was supported in part by a grant of the 2009 BK21 Project for Applied Pharmaceutical Life Sciences and by the Korean Health 21 R&D project, Ministry of Health & Welfare, Korea (A050376).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Hepatic and intestinal CYP2C11 and 3A subfamily
Pharmacokinetics
Rats with liver cirrhosis and/or diabetes mellitus
Sildenafil and N-desmethylsildenafil

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10.3109/00498254.2010.532885

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title = "Pharmacokinetics of sildenafil and its metabolite, N-desmethylsildenafil, in rats with liver cirrhosis and diabetes mellitus, alone and in combination",

abstract = "Pharmacokinetics of sildenafil and its metabolite, N-desmethylsildenafil, in humans and rats with liver cirrhosis (LC) and diabetes mellitus (DM), alone and in combination (LCD) did not seem to be reported. Sildenafil was administered intravenously (10mg/kg) and orally (20mg/kg) to control, LC, DM, and LCD rats. Expression of intestinal CYP isozymes in those rats was also measured. In LC, DM, and LCD rats, the areas under the curve (AUCs) of intravenous sildenafil were significantly greater (by 195\%, 54.2\%, and 127\%, respectively) than controls. In LC and LCD rats, AUCs of oral sildenafil were significantly greater (3010\% and 2030\%, respectively) than controls. In LC, DM, and LCD rats, significantly greater AUCs of intravenous sildenafil were due to the slower hepatic extraction of sildenafil (because of decrease in the protein expression of hepatic CYP2C11 and 3A subfamily in LC and LCD rats, and CYP2C11 in DM rats). In LC and LCD rats, greater magnitude of increase in AUCs of oral sildenafil than those after the intravenous administration could be mainly due to the decrease in the intestinal extraction of sildenafil (because of decrease in the protein expression of intestinal CYP2C11 in LC and LCD rats).",

keywords = "Hepatic and intestinal CYP2C11 and 3A subfamily, Pharmacokinetics, Rats with liver cirrhosis and/or diabetes mellitus, Sildenafil and N-desmethylsildenafil",

author = "Ahn, \{C. Y.\} and Bae, \{S. K.\} and Bae, \{S. H.\} and Kang, \{H. E.\} and Kim, \{S. H.\} and Lee, \{M. G.\} and Shin, \{W. G.\}",

note = "Funding Information: This study was supported in part by a grant of the 2009 BK21 Project for Applied Pharmaceutical Life Sciences and by the Korean Health 21 R\&D project, Ministry of Health \& Welfare, Korea (A050376).",

year = "2011",

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doi = "10.3109/00498254.2010.532885",

language = "English",

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T1 - Pharmacokinetics of sildenafil and its metabolite, N-desmethylsildenafil, in rats with liver cirrhosis and diabetes mellitus, alone and in combination

AU - Ahn, C. Y.

AU - Bae, S. K.

AU - Bae, S. H.

AU - Kang, H. E.

AU - Kim, S. H.

AU - Lee, M. G.

AU - Shin, W. G.

N1 - Funding Information: This study was supported in part by a grant of the 2009 BK21 Project for Applied Pharmaceutical Life Sciences and by the Korean Health 21 R&D project, Ministry of Health & Welfare, Korea (A050376).

PY - 2011/2

Y1 - 2011/2

N2 - Pharmacokinetics of sildenafil and its metabolite, N-desmethylsildenafil, in humans and rats with liver cirrhosis (LC) and diabetes mellitus (DM), alone and in combination (LCD) did not seem to be reported. Sildenafil was administered intravenously (10mg/kg) and orally (20mg/kg) to control, LC, DM, and LCD rats. Expression of intestinal CYP isozymes in those rats was also measured. In LC, DM, and LCD rats, the areas under the curve (AUCs) of intravenous sildenafil were significantly greater (by 195%, 54.2%, and 127%, respectively) than controls. In LC and LCD rats, AUCs of oral sildenafil were significantly greater (3010% and 2030%, respectively) than controls. In LC, DM, and LCD rats, significantly greater AUCs of intravenous sildenafil were due to the slower hepatic extraction of sildenafil (because of decrease in the protein expression of hepatic CYP2C11 and 3A subfamily in LC and LCD rats, and CYP2C11 in DM rats). In LC and LCD rats, greater magnitude of increase in AUCs of oral sildenafil than those after the intravenous administration could be mainly due to the decrease in the intestinal extraction of sildenafil (because of decrease in the protein expression of intestinal CYP2C11 in LC and LCD rats).

AB - Pharmacokinetics of sildenafil and its metabolite, N-desmethylsildenafil, in humans and rats with liver cirrhosis (LC) and diabetes mellitus (DM), alone and in combination (LCD) did not seem to be reported. Sildenafil was administered intravenously (10mg/kg) and orally (20mg/kg) to control, LC, DM, and LCD rats. Expression of intestinal CYP isozymes in those rats was also measured. In LC, DM, and LCD rats, the areas under the curve (AUCs) of intravenous sildenafil were significantly greater (by 195%, 54.2%, and 127%, respectively) than controls. In LC and LCD rats, AUCs of oral sildenafil were significantly greater (3010% and 2030%, respectively) than controls. In LC, DM, and LCD rats, significantly greater AUCs of intravenous sildenafil were due to the slower hepatic extraction of sildenafil (because of decrease in the protein expression of hepatic CYP2C11 and 3A subfamily in LC and LCD rats, and CYP2C11 in DM rats). In LC and LCD rats, greater magnitude of increase in AUCs of oral sildenafil than those after the intravenous administration could be mainly due to the decrease in the intestinal extraction of sildenafil (because of decrease in the protein expression of intestinal CYP2C11 in LC and LCD rats).

KW - Hepatic and intestinal CYP2C11 and 3A subfamily

KW - Pharmacokinetics

KW - Rats with liver cirrhosis and/or diabetes mellitus

KW - Sildenafil and N-desmethylsildenafil

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DO - 10.3109/00498254.2010.532885

M3 - Article

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AN - SCOPUS:78651367391

SN - 0049-8254

VL - 41

SP - 164

EP - 174

JO - Xenobiotica

JF - Xenobiotica

IS - 2

ER -

Pharmacokinetics of sildenafil and its metabolite, N-desmethylsildenafil, in rats with liver cirrhosis and diabetes mellitus, alone and in combination

Abstract

Bibliographical note

UN SDGs

Keywords

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