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Uptake of catamphiphilic drugs into erythrocytes and muscular tissue correlates to membrane enrichment and to45Ca displacement from phosphatidylserine monolayers

Scheufler, E., Vogelgesang, R., Wilffert, B., Pegram, B. L., Hunter, J. B., Wermelskirchen, D. & Peters, T., 22-Oct-1990, In : Journal of Pharmacology and Experimental Therapeutics. 252, 1, p. 333-338 6 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • E. Scheufler
  • R. Vogelgesang
  • B. Wilffert
  • B.L. Pegram
  • J.B. Hunter
  • D. Wermelskirchen
  • Thies Peters
The uptake of the catamphiphilic drugs flunarizine, R 56865 [N-1-4-(4-fluorophenoxy)butyl-4-piperidinyl-N-methyl-2-benzothia- zolamine], 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°C. The uptake was concentration proportional between 10-8and 10-6mol/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°C). Equilibrium was reached after 360 min and the tissue/medium ratio (T/M) was concentration proportional between 10-8and 10-6mol/l for all drugs. E/M or T/M ratios, respectively, increased in the order: erythrocytes <aortas <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 EC50for45Ca displacement from phosphatidylserine monolayers, but were poorly correlated with the octanol-water coefficient of the uncharged molecules. The EC50for45Ca 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.
Original languageEnglish
Pages (from-to)333-338
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume252
Issue number1
Publication statusPublished - 22-Oct-1990

    Keywords

  • calcium, diltiazem, flunarizine, lidocaine, n [1 [4 (4 fluorophenoxy)butyl] 4 piperidinyl] n methyl 2 benzothiazolamine, nitrendipine, phosphatidylserine, radioisotope, verapamil, animal cell, article, drug uptake, erythrocyte membrane, heart left atrium, human, human cell, lipid membrane, male, nonhuman, priority journal, rat, thoracic aorta

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