An in vitro approach to study cellular kinetics of drugs.
We adapted different existing techniques in order to optimize the methodology for studying kinetic interactions between drugs and cells in vitro. Using the polymorphonuclear leukocyte as a target cell, we measured the binding of various ligands and intracellular drug concentrations. We also studied pharmacological modulation of drug transport under normal and inflammatory conditions. Our approach allows reproducible measurements on ligands with low affinity for association sites on polymorphonuclear leukocytes. We present data for various nonsteroidal antiinflammatory drugs and other ligands to validate our methodological approach. On the basis of the results thus obtained, we proposed a tentative model to fit data and concepts of drug-cell interactions.
Raghoebar
M
M
Department of Pharmacology, University of Nijmegen, The Netherlands.
Huisman
J A
JA
Van den Berg
W B
WB
Van Ginneken
C A
CA
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D008954:Models, Biological; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000493:pharmacokinetics; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008024:Ligands; D009240:N-Formylmethionine Leucyl-Phenylalanine