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标题：Uptake of Basic Drugs into Rat Lung Granule Fraction in Vitro
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作者：Junko ISHIZAKI ; Koichi YOKOGAWA ; Emi NAKASHIMA 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1998
卷号：21
期号：8
页码：858-861
DOI：10.1248/bpb.21.858
出版社：The Pharmaceutical Society of Japan
摘要：Although basic drugs are distributed wiedely in various tissues, they are characteristically concentrated in the lung granule fraction. We examined the uptake of seven lipophilic basic drugs into rat lung granule fraction (P₂) in vitro and investigated the contributions of drug lipophilicity and lysosomal trapping to the characteristic lung P₂ distribution. The uptake of each drug into P₂ was examined at various pH values. The drug concentration in P₂ was determined by gas chromatography. Biperiden (BP) was rapidly taken up into P₂, reaching a maximal concentration within 1 min at pH 7.4 at both 4°Cand 37°C. Both BP and chlorpromazine uptake into P₂, was biphasic. Though the uptake rates of the seven drugs into P₂ increased with rising pH, the rate of increase varied for each drug. There was a good correlation between the octanol-water partition coefficient of the non-ionized form (P_oct) of each drug and the uptake into P₂ in the presence or absence of NH₄Cl, which inhibits lysosomal tarpping. However, uptake into P₂ in the presence of NH₄Cl showed a stronger P_oct-dependency. We conclude that the distribution of basic drugs into lung P₂ is dependent on both drug lipophilicity and lysosomal uptake.
关键词：basic drug;rat lung granule fraction;lipophilicity;distribution;lysosome