Uptake of Basic Drugs into Rat Lung Granule Fraction in Vitro

概要

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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 (P_2) in vitro and investigated the contributions of drug lipophilicity and lysosomal trapping to the characteristic lung P_2 distribution. The uptake of each drug into P_2 was examined at various pH values. The drug concentration in P_2 was determined by gas chromatography. Biperiden (BP) was rapidly taken up into P_2,reaching a maximal concentration within 1 min at pH 7.4 at both 4℃and 37℃. Both BP and chlorpromazine uptake into P_2,was biphasic. Though the uptake rates of the seven drugs into P_2 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 P_2 in the presence or absence of NH_4Cl, which inhibits lysosomal tarpping. However, uptake into P_2 in the presence of NH_4Cl showed a stronger P_<oct>-dependency. We conclude that the distribution of basic drugs into lung P_2 is dependent on both drug lipophilicity and lysosomal uptake.
公益社団法人日本薬学会の論文
1998-08-15