Plasma Protein Binding of Quinine: Binding to Human Serum Albumin, α1-Acid Glycoprotein and Plasma from Patients with Malaria

Author:

Wanwimolruk Sompon1,Denton John R1

Affiliation:

1. School of Pharmacy, University of Otago, PO Box 913, Dunedin, New Zealand

Abstract

Abstract The binding of quinine to human serum albumin (HSA), α1-acid glycoprotein (AAG) and plasma obtained from healthy subjects (10 Caucasians and 15 Thais) and from Thai patients with falciparum malaria (n = 20) has been investigated. In healthy volunteers, plasma protein binding expressed as the percentage of unbound quinine was 7·9–31·0% (69–92·1% bound). The mean percentage of unbound quinine found with essentially fatty acid-free HSA (40 g L−1) was 65·4±1 −5% (mean±s.d.) and was comparable with the value (66·3 ± 3·8%, mean ± s.d.) for Fraction V HSA (40 g L−1)- This suggests that fatty acids do not influence the plasma protein binding of quinine. Binding of quinine to 0·7 g L−1 AAG was high (mean unbound 61·0 ± 5·0%), indicating that quinine is bound primarily to AAG and albumin, although other plasma proteins such as lipoproteins may be involved. The mean percentage of unbound quinine was slightly less in Caucasians (14·8 ± 6·7% unbound), compared with healthy Thai subjects (17·0 ± 6·7% unbound). The higher binding of quinine in Caucasian subjects was associated with a higher plasma AAG concentration observed in Caucasians. Mean percentage of unbound quinine was significantly lower in Thai patients with malaria (10·9 ± 4·0%) than in the healthy Thai subjects. The increase in the extent of quinine binding corresponded with the increase in the acute-phase reactant protein, AAG in the patients with malaria. Overall, when the data were combined there was a significant correlation (r = 0·846, P < 0·005) between the binding ratio (bound/unbound) of quinine and the plasma AAG concentration. This suggests that plasma AAG concentration may serve as a useful index to predict alterations in quinine binding. Although quinine is bound to albumin, it was not bound to either site I or site II on HSA as indicated from equilibrium dialysis and fluorescent probe displacement studies. Binding displacement studies revealed that there was no marked displacement of quinine by a variety of highly bound acidic and basic drugs, including other antimalarial drugs at their therapeutic concentrations.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

Reference29 articles.

1. Albumin as a specific binding protein for drugs and endogenous compounds;Birkett,1986

2. The colorimetric micro-determination of non-esterified fatty acids in plasma;Duncombe;Clin. Chim. Acta,1964

3. Factors affecting quinidine protein binding in humans;Edwards;J. Pharm. Sci.,1984

4. Increased plasma binding of quinidine after surgery: a preliminary report;Fremstad;Eur. J. Clin. Pharmacol.,1976

5. The location of drug binding sites in human serum albumin;Fehske;Biochem. Pharmacol.,1981

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3