Binding of drugs to muscle tissue: dependence on drug concentration and lipid content of tissue.
For a series of 16 drugs the extent of binding to homogenized rabbit skeletal muscle was determined by means of ultrafiltration. The percent bound of basic drugs was essentially constant over a 100- to 1000-fold concentration range, i.e., binding was linear. Among weak organic acids the fraction bound decreased with increasing drug concentration for furosemide, warfarin, phenylbutazone, salicyclic acid and sulfonamides. Fitting of the binding data by Langmuir isotherms appeared to be inappropriate for several reasons. A simple power function (Freundlich isotherm) was found to satisfactorily represent the experimental data. Drug binding properties of muscle homogenate were altered following extraction of lipids with acetone. Lipid-depleted muscle tissue exhibited a decrease in binding of chlorpromazine and propranolol, whereas binding of imipramine was unchanged. Binding of phenytoin, warfarin and sulfadimethoxine was enhanced in lipid-depleted muscle. The results suggest that binding of drugs to muscle tissue cannot solely be explained in terms of partitioning into lipids.
D000818:Animals; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D050356:Lipid Metabolism; D008954:Models, Biological; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011817:Rabbits
D004364:Pharmaceutical Preparations; D010743:Phospholipids