In Vitro Binding of Drugs to Colestipol Hydrochloride
| Autor: | Howard Ko, Max E. Royer |
|---|---|
| Rok vydání: | 1974 |
| Předmět: |
Taurocholic Acid
Time Factors Polymers Cholestyramine Resin Pharmaceutical Science Oleic Acids Pharmacology Micelle chemistry.chemical_compound Tetracycline Hydrochloride food Ethers Cyclic Colestipol Hydrochloride Polyamines medicine Vitamin A Vitamin a1 Binding Sites Chromatography Cholestyramine Aspirin Anticholesteremic Agents Osmolar Concentration Hydrogen-Ion Concentration Ascorbic acid Lincomycin Hydrochloride Oleic acid Cholesterol Solubility chemistry Phenobarbital Spectrophotometry Ultraviolet food.nutrient medicine.drug |
| Zdroj: | Journal of Pharmaceutical Sciences. 63:1914-1920 |
| ISSN: | 0022-3549 |
| Popis: | The in vitro binding of drugs by colestipol hydrochloride depended not only upon ionic strength, pH, and type of competing ion but also upon whether association could occur with other molecules. Where feasible, the initial input ratio of drug to binding agent was equivalent to that if both were administered orally in therapeutically effective amounts. The water-soluble drugs chlorpropamide-35S, niacin-6-14C, ascorbic acid, aspirin, salicylic acid, phenobarbital-14C, sulfadiazine, penicillin G, and lincomycin hydrochloride were less than 30% bound to colestipol hydrochloride in tromethamine–sodium chloride buffer (pH 7.5, μ = 0.15), while warfarin and tetracycline hydrochloride were bound 59 and 30%, respectively. The binding of a drug determined under these conditions is an estimate of the upper limit of the percentage of the dose of orally ingested drug that would remain bound in vivo. The binding of tetracycline hydrochloride, sulfadiazine, benzyl penicillin, and lincomycin hydrochloride to colestipol hydrochloride was reversible, and only a small fraction of warfarin was irreversibly bound to colestipol hydrochloride. As a positive control, binding of the drugs (or bile salts) to cholestyramine was also studied. Cholestyramine bound most of the drugs investigated to a greater extent than did colestipol hydrochloride. The binding of water-soluble drugs to colestipol hydrochloride decreased in the combined presence of monoolein, oleic acid, and taurocholate. The colestipol hydrochloride binding of compounds of low aqueous solubility, vitamins A1, D2, and K1, and cholesterol-14C increased as the concentration of taurocholate decreased. Monoolein increased, while oleic acid decreased, the binding of taurocholate to colestipol hydrochloride. Oleic acid increased slightly the binding of taurocholate to cholestyramine; monoolein had no effect. The data are consistent with the hypotheses that: (a) taurocholate associates with and thus transfers compounds of low aqueous solubility to polymer binding sites, (b) the fraction of vitamin A1 and cholesterol-14C associated with the polymer binding sites and the fraction in solution depends upon the concentration of taurocholate, and (c) the binding of taurocholate depends upon the composition of micelle formed. |
| Databáze: | OpenAIRE |
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