肝素引起的非脂肪酸调节的药物结合变化。

Nonfatty acid-modulated variations in drug binding due to heparin.

作者信息

Naranjo C A, Khouw V, Sellers E M

出版信息

Clin Pharmacol Ther. 1982 Jun;31(6):746-52. doi: 10.1038/clpt.1982.105.

DOI:10.1038/clpt.1982.105

Abstract

Changes in free fatty acids (FFAs) do not always correlate with variations in drug binding. To dissociate heparin effects on FFAs and drug binding, six healthy fasting subjects received 50 units (USP) IV heparin (Harris L932) with and without protamine (3.2 mg IV). Protamine completely suppressed heparin-induced rises in FFAs and warfarin free fraction (W alpha), but diazepam free fraction (D alpha) increased (P less than 0.005). In vitro, increasing concentrations of heparin added to serum increased D alpha (P less than 0.0005) and W alpha (P less than 0.005) without changing FFAs. In eight subjects given 50 units IV heparin (Harris L014), FFAs (P less than 0.001) and propranolol free fraction (P alpha) rose (P less than 0.01), but variations in FFAs and P alpha did not correlate (r = 0.18). When two different heparin lots (Harris L014 and Organon LA39) were tested in vivo. Harris L014 heparin increased FFAs (P less than 0.005) and P alpha (P less than 0.0005), but variations in FFAs and P alpha correlated poorly (r = 0.43, P less than 0.05). In contrast, the Organon LA39 heparin did not change FFAs, but did increase P alpha (P less than 0.0005); variations in FFAs and P alpha did not correlate (r = 0.22). These results indicate that heparin-induced variations in drug binding are not exclusively related to changes in FFAs.

摘要

游离脂肪酸（FFAs）的变化并不总是与药物结合的变化相关。为了区分肝素对FFAs和药物结合的影响，六名健康的空腹受试者接受了50单位（美国药典）静脉注射肝素（Harris L932），其中部分受试者同时接受了鱼精蛋白（3.2毫克静脉注射）。鱼精蛋白完全抑制了肝素诱导的FFAs升高以及华法林游离分数（Wα）升高，但地西泮游离分数（Dα）升高（P<0.005）。在体外，向血清中添加浓度不断增加的肝素会使Dα升高（P<0.0005）和Wα升高（P<0.005），而FFAs不变。在八名接受50单位静脉注射肝素（Harris L014）的受试者中，FFAs升高（P<0.001），普萘洛尔游离分数（Pα）升高（P<0.01），但FFAs和Pα的变化不相关（r=0.18）。当在体内测试两种不同批次的肝素（Harris L014和Organon LA39）时，Harris L014肝素使FFAs升高（P<0.005）和Pα升高（P<0.0005），但FFAs和Pα的变化相关性较差（r=0.43，P<0.05）。相比之下，Organon LA39肝素未改变FFAs，但使Pα升高（P<0.0005）；FFAs和Pα的变化不相关（r=0.22）。这些结果表明，肝素诱导的药物结合变化并非完全与FFAs的变化相关。