Absorption, Distribution, Metabolism, and Excretion of the Novel Helicase-Primase Inhibitor, Amenamevir (ASP2151), in Rodents

European Journal of Drug Metabolism and Pharmacokinetics
Yoshiaki OhtsuKiyoshi Noguchi

Abstract

The helicase-primase inhibitor amenamevir (ASP2151) is a novel therapeutic agent which has been approved for the treatment of herpes zoster. The present study examined the pharmacokinetic profile of amenamevir in rodents and compared it with data from the literature of past and current established therapies (acyclovir and valaciclovir) to provide additional data to facilitate drug discovery and proper drug use. In situ absorption, blood and plasma radioactivity concentrations, tissue distribution, and excretion were determined using liquid scintillation counting. Plasma amenamevir concentrations were measured using a validated chromatographic method. Chemical structures of in vivo metabolites were investigated using liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. Amenamevir, after single intravenous administration to mice, had an elimination half-life of 2 h. Bioavailability was 40% after single oral administration. In situ absorption data indicated that amenamevir is mainly absorbed in the small intestine. The main component in mouse plasma was amenamevir, accounting for 87.9% of amenamevir-derived components. Our results suggest that the main elimination pathway in mice is oxidative metabo...Continue Reading

References

Jul 20, 1982·The American Journal of Medicine·S S Good, P de Miranda
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Dec 31, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jie LingChandra Prakash
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Feb 12, 2015·Clinical Pharmacology and Therapeutics·S H JamesM N Prichard
Jun 21, 2015·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Yoshiaki OhtsuKiyoshi Noguchi

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Citations

Apr 3, 2019·Journal of Medicinal Chemistry·Andrew C FlickChristopher J O'Donnell

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Methods Mentioned

BETA
urine collection
nuclear magnetic resonance
NMR

Software Mentioned

WinNonlin

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