Binding of thiopental to human serum albumin in the presence of halogenated hydrocarbons and ethers.
Thiopental binding (substrate concentration 0.04.10(-3) M = 10 micrograms/ml) to 1% human serum albumin (HSA) studied by equilibrium dialysis in 1/15 M phosphate buffer solution (pH 7.4) was increased significantly from 40.2% (= control) to 55% in the presence of 4.71.10(-3) M halothane (= 11.36 vol%); 1.18.10(-3) M = 2.84 vol% halothane caused a lesser but still significant increase (vs. control) of thiopental binding. This halothane effect on the binding of thiopental to HSA was studied under several experimental conditions (variation of thiopental concentration, HSA concentration, pH of the buffer solution, temperature). Other halogenated hydrocarbons such as chloroform (6.2.10(-3) M) and carbon tetrachloride (5.2.10(-3) M) also markedly increased the binding of thiopental to HSA as compared to the control (percentage of fraction bound, 53 and 61%, respectively); the same effect, but to a lesser extent, was obtained under the influence of three halogenated ethers, i.e., enflurane (4.1.10(-3) M--greater than 45% thiopental bound), isoflurane (4.1.10(-3) M--greater than 50% bound) and methoxyflurane (4.3.10(-3) M--greater than 47% bound). Under the same experimental conditions, ethanol (up to 8.9.10(-2) M) and diethylether (up to 4.9.10(-2) M) did not increase the percentage of thiopental bound to HSA.
Büch
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Institut für Anästhesie, Universität des Saarlandes, Homburg/Saar, FRG.
Altmayer
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Büch
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HP
D002251:Carbon Tetrachloride / Q000494:pharmacology; D002725:Chloroform / Q000494:pharmacology; D004737:Enflurane / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D004986:Ether / Q000494:pharmacology; D004987:Ethers / Q000494:pharmacology*; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007530:Isoflurane / Q000494:pharmacology; D008733:Methoxyflurane / Q000494:pharmacology; D008970:Molecular Weight; D011485:Protein Binding / Q000187:drug effects; D012709:Serum Albumin / Q000378:metabolism*; D013696:Temperature; D013874:Thiopental / Q000097:blood*
D004987:Ethers; D006846:Hydrocarbons, Halogenated; D012709:Serum Albumin; D004986:Ether; D008733:Methoxyflurane; D000431:Ethanol; D002725:Chloroform; D004737:Enflurane; D002251:Carbon Tetrachloride; D007530:Isoflurane; D013874:Thiopental