The antimalarial drug halofantrine is bound mainly to low and high density lipoproteins in human serum
Autor: | R Brandt, B Cenni, J Meyer, B Betschart |
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Rok vydání: | 1995 |
Předmět: |
Very low-density lipoprotein
Erythrocytes Blotting Western Orosomucoid chemistry.chemical_compound Halofantrine Animals Humans Pharmacology (medical) Binding site Whole blood Pharmacology chemistry.chemical_classification Binding Sites biology Albumin Blood Proteins Phenanthrenes Blood proteins Lipoproteins LDL Molecular Weight chemistry Biochemistry Chromatography Gel biology.protein Electrophoresis Polyacrylamide Gel Lipoproteins HDL Glycoprotein Research Article |
Zdroj: | British Journal of Clinical Pharmacology. 39:519-526 |
ISSN: | 0306-5251 |
Popis: | 1. The major serum proteins which bind halofantrine were identified by size exclusion chromatography. In addition, the binding affinity of halofantrine to human erythrocytes and serum proteins was measured by an erythrocyte partitioning technique. The influence of serum-drug binding on the distribution of halofantrine in whole blood was estimated by simulating several disease-related changes in the levels of the most important binding proteins. 2. The chromatographic resolution of serum preincubated with halofantrine allowed a quantitative analysis of binding to low density lipoproteins, high density lipoproteins, alpha 1-acid glycoprotein and albumin using the erythrocyte partitioning technique. Very low density lipoproteins did not bind halofantrine to a significant extent. 3. In whole blood halofantrine is bound to serum proteins (83%) and to erythrocytes (17%). Low density lipoproteins (affinity constant nKP = 44.4 l g-1) and high density lipoproteins (nKP = 14.4 l g-1) were the most important binding proteins in serum. alpha 1-acid glycoprotein (nKP = 4.39 l g-1) and albumin (nKP = 0.27 l g-1) had relatively low binding affinities. 4. The concentration of serum proteins influences both the fraction of unbound drug and the fraction of drug associated with the erythrocytes. Changes in serum protein concentrations often encountered in malaria are likely to increase both the unbound fraction and the fraction bound to the erythrocytes. |
Databáze: | OpenAIRE |
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