Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Uptake of Basic Drugs into Rat Lung Granule Fraction in Vitro
Junko ISHIZAKIKoichi YOKOGAWAEmi NAKASHIMAShoji OHKUMAFujio ICHIMURA
Author information
JOURNAL FREE ACCESS

1998 Volume 21 Issue 8 Pages 858-861

Details
Abstract

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 (Poct) 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 Poct-dependency. We conclude that the distribution of basic drugs into lung P2 is dependent on both drug lipophilicity and lysosomal uptake.

Content from these authors
© The Pharmaceutical Society of Japan
Previous article Next article
feedback
Top