The Effect of Divalent Cations on the Membrane Properties and Pharmacokinetics in Rat of the Lipid A Analogue E5531-Reference-Cited by-同舟云学术

The Effect of Divalent Cations on the Membrane Properties and Pharmacokinetics in Rat of the Lipid A Analogue E5531

Published:2000-01 Issue:1 Volume:52 Page:39-45
ISSN:0022-3573
Container-title:Journal of Pharmacy and Pharmacology
language:en
Short-container-title:

Author:

Asai Yasuyuki¹,Sano Yoshihisa²,Kikuchi Kiyomi²,Iwamoto Kiyoshi¹,Watanabe Sumio²

Affiliation:

1. Formulation Research Laboratory, Kawashima, Eisai Co., Ltd, Takehaya-machi, Kawashima-cho, Hashima-gun, Gifu 501-6195, Japan

2. Tsukuba Research Laboratories, Eisai Co., Ltd, Tokodai, Tsukuba, Ibaraki 300-2635, Japan

Abstract

Abstract To obtain information on the effects of Ca2+ on the membrane properties of the lipid A analogue E5531, we have determined the aggregate size, zeta potential, membrane fluidity, micropolarity and permeability of the E5531 membrane as a function of Ca2+ levels. Within the molar ratios of [Ca2+]/[E5531] = 1 and 3, Ca2+ increased the zeta potential of the E5531 membrane but had no effect on aggregate size (approximately 20 nm). Within the above ratios, Ca2+ decreased the membrane fluidity, as measured by micropolarity of E5531 and increased the phase transition temperature. The pharmacokinetics in rats for these samples with different membrane fluidity, prepared by changing the pre-dose formulation concentration of Ca2+, was determined and a correlation between membrane fluidity and pharmacokinetics was clearly observed. It thus appears that Ca2+ effects the membrane fluidity of E5531 as well as its pharmacokinetics in rats.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

Link

http://academic.oup.com/jpp/article-pdf/52/1/39/36784361/0022357001773661.pdf

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