RT Journal Article
SR Electronic
T1 Uptake of catamphiphilic drugs into erythrocytes and muscular tissue correlates to membrane enrichment and to 45Ca displacement from phosphatidylserine monolayers.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 333
OP 338
VO 252
IS 1
A1 E Scheufler
A1 R Vogelgesang
A1 B Wilffert
A1 B L Pegram
A1 J B Hunter
A1 D Wermelskirchen
A1 T Peters
YR 1990
UL http://jpet.aspetjournals.org/content/252/1/333.abstract
AB The uptake of the catamphiphilic drugs flunarizine, R 56865 [N-1-4-(4-fluorophenoxy)butyl-4-piperidinyl-N-methyl-2- benzothiazolamine], verapamil, diltiazem, lidocaine and the noncatamphiphilic drug nitrendipine into erythrocytes and erythrocyte membranes was measured at pH 7.2 in a Ringer's solution at 22 degrees C. The uptake was concentration proportional between 10(-8) and 10(-6) mol/l for all drugs investigated; the erythrocyte/medium ratio (E/M) was constant after 20 min in all experiments. In rat aortas and left atria drug uptake was measured in a 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffered medium (pH 7.2, 32 degrees C). Equilibrium was reached after 360 min and the tissue/medium ratio (T/M) was concentration proportional between 10(-8) and 10(-6) mol/l for all drugs. E/M or T/M ratios, respectively, increased in the order: erythrocytes less than aortas less than left atria. However, the particular drug/phospholipid ratios were relatively constant for the drugs investigated, indicating that the membranes were a major distribution phase for these drugs. For the catamphiphilic drugs, the E/M or T/M ratios correlated linearly with the EC50 for 45Ca displacement from phosphatidylserine monolayers, but were poorly correlated with the octanol-water coefficient of the unchanged molecules. The EC50 for 45Ca displacement from phosphatidylserine monolayers is a measure for the uptake of the protonated species of catamphiphilic drugs into erythrocytes or tissue and may be a good estimate of tissue uptake of these drugs in general.