THE ANTIMALARIAL DRUG HALOFANTRINE IS BOUND MAINLY TO LOW AND HIGH-DENSITY-LIPOPROTEINS IN HUMAN SERUM

被引:30
作者
CENNI, B
MEYER, J
BRANDT, R
BETSCHART, B
机构
[1] SWISS TROP INST,DEPT MED PARASITOL,CH-4002 BASEL,SWITZERLAND
[2] F HOFFMANN LA ROCHE & CO LTD,DEPT PHARMACOKINET,CH-4002 BASEL,SWITZERLAND
关键词
HALOFANTRINE; PLASMODIUM FALCIPARUM; MALARIA; PHARMACOKINETICS; SERUM PROTEIN BINDING;
D O I
10.1111/j.1365-2125.1995.tb04489.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 nK(P) 44.4 1 g(-1)) and high density lipoproteins (nK(P) = 14.4 1 g(-1)) were the most important binding proteins in serum. alpha 1-acid glycoprotein (nK(P) = 4.39 1 g(-1)) and albumin (nK(P) = 0.27 1 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.
引用
收藏
页码:519 / 526
页数:8
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