UPTAKE OF BASIC DRUGS INTO RAT LUNG GRANULE FRACTION IN-VITRO

Although basic drugs are distributed widely in various tissues, they a re characteristically concentrated in the lung granule fraction. We ex amined the uptake of seven lipophilic basic drugs into rat lung granul e fraction (P-2) in vitro and investigated the contributions of drug l ipophilicity and lysosomal trapping to the characteristic lung P-2 dis tribution. The uptake of each drug into P-2 was examined at various pH values. The drug concentration in P-2 was determined by gas chromatog raphy. Biperiden (BP) mas rapidly taken up into P-2, reaching a maxima l concentration within 1 min at pH 7.4 at both 4 degrees C and 37 degr ees C. Both BP and chlorpromazine uptake into P-2 was biphasic. Though the uptake rates of the seven drugs into P-2 increased with rising: p H, the rate of increase varied for each drug. There was a good correla tion between the octanol-water partition coefficient of the nonionized form (P-oct) of each drug and the uptake into P-2 in the presence or absence of NH4Cl, which inhibits lysosomal trapping. However, uptake i nto P-2 in the presence of NH4Cl showed a stronger P-oct-dependency, W e conclude that the distribution of basic drugs into lung P-2 is depen dent on both drug lipophilicity and lysosomal uptake.