Membrane solubility of chlorpromazine. Hygroscopic desorption and centrifugation methods yield comparable results

Abstract

Binding of the positively charged drug chlorpromazine to artificial and erythrocyte bilayer membranes was investigated by the filtration method called hygroscopic desorption [Conrad & Singer (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 5202-5206] and by the conventional centrifugation method. Only minor differences in the partition coefficients were observed using the two methods. Our finding is not consistent with the observation of Conrad & Singer that amphipaths are completely excluded from biological membranes. However, the partition coefficient is dependent on membrane composition, which means dependent on the physical properties of a membrane.

A Fast and reliable spectroscopic method for the determination of membrane‐water partition coefficients of organic compounds

“…EPC, egg yolk phosphatidylcholine. [14] Equations 10 and 12 can be rearranged to yield a linear relation between [1/(D w − D t )] and (1/C L ): [15] and from a plot of [1/(D w − D t )] vs. 1/C L , the intercept is [1/(D w − D m )], and the slope allows for the determination of K p T . Again, the linear form (Eq.…”

“…Several methods have been devised to measure partition coefficients, namely, ultracentrifugation (4,9), hygroscopic desorption (14,15), microdialysis (6), chromatography (7,8), fluorimetry (10), and spectrophotometry (11)(12)(13)16). As most methods rely on phase separation, a process that can disturb the equilibrium state of the samples (12,13), it is of great interest to develop methods that may circumvent this time-consuming process.…”

Chlorpromazine: A Drug Potentially Useful for Treating Mycobacterial Infections

“…Its partition coefficient for erythro cytes, for instance, is between 3,000 and 5,000 [31]. It concentrates in organs like the lungs, liver, kidneys, and brain [32], in cell mem branes from 200-to 500-fold, and in phospho lipid organelles at up to 1,500-fold [29].…”

“…No published data to directly support this obser vation have been found. However, there are many data showing that CPZ has a strong af finity for cells and tissues, and especially for cell membranes and phospholipid organelles [28][29][30]. Its partition coefficient for erythro cytes, for instance, is between 3,000 and 5,000 [31].…”

Effect of Phosphatidylserine Content on the Partition Coefficients of Diazepam and Flurazepam between Phosphatidylcholine-Phosphatidylserine Bilayer of Small Unilamellar Vesicles and Water Studied by Second Derivative Spectrophotometry.

“…Determination of the partition coefficients of drugs in liposome/buffer systems has usually been accompanied by separation procedures of centrifugation, 4,5,7,16) filtration 17) or membrane dialysis 6,8,9) before measuring the concentration of free drugs or the amount of bound drugs. However, these separation procedures are troublesome and may disturb the equilibrium states of the sample solutions and also lead to errors arising from non-specific matrix adsorption of drugs onto membranes.…”