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Evaluation for effect of hypothermia on the disposition of 4-nitrophenol in rats by in-vitro metabolism study and rat liver perfusion system


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Title: Evaluation for effect of hypothermia on the disposition of 4-nitrophenol in rats by in-vitro metabolism study and rat liver perfusion system
Authors: Miyamoto, Hirotaka / Matsueda, Satoshi / Komori, Kotaro / Fumoto, Shintaro / Nakashima, Mikiro / Yoshikawa, Naoki / Hirata, Haruna / Shimokawa, Kenta / Ohwaki, Yuichi / Nishida, Koyo
Issue Date: Oct-2013
Publisher: Pharmaceutical Press
Citation: Journal of Pharmacy and Pharmacology, 65(10), pp.1536-1540; 2013
Abstract: Objectives The aim of this study was to evaluate the effect of hypothermia on the in-vivo pharmacokinetics of 4-nitrophenol (4NP) using rat liver homogenate and rat liver perfusion system. Methods Rat liver homogenate was incubated with 4NP, which is mainly metabolized by cytochrome P450 2E1, at 37, 34, 32 or 28°C. The Michaelis constant (Km) and maximum elimination velocity (Vmax) of 4NP were calculated by a Hanes-Woolf plot. The hepatic extraction ratio (Eh) of 4NP was evaluated in a rat liver perfusion study at 37, 34, 32 or 28°C. Moreover, the plasma concentration profiles of 4NP after its intravenous (i.v.) administration to rats were analysed by the moment theory and were compared with in-vitro parameters. Key findings While the Km of 4NP was not changed, the Vmax and Eh were reduced at low temperatures. The plasma concentrations of 4NP after its i.v. administration to rats were significantly increased at 28°C. Conclusion Changes in the pharmacokinetics of 4NP under hypothermic conditions were caused by alterations in Vmax and E h. We may be able to predict the disposition of a drug by in-vitro studies.
Keywords: 4-nitrophenol / cytochrome P450 2E1 / hypothermia / liver perfusion
URI: http://hdl.handle.net/10069/35851
ISSN: 00223573
DOI: 10.1111/jphp.12130
Rights: © 2013 Royal Pharmaceutical Society. / This is the peer reviewed version of the following article: Journal of Pharmacy and Pharmacology, 65(10), pp.1536-1540; 2013, which has been published in final form at http://dx.doi.org/10.1111/jphp.12130 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/35851

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