Abstract Number: PB0032
Meeting: ISTH 2021 Congress
Background: Recent primate studies have suggested that when bovine and porcine heparins are dosed on the basis of equivalent anti-Xa units, equivalent anti-IIa and anti-Xa responses are observed. The pharmacokinetic behavior of heparins has traditionally been based on antithrombin-dependent anti-Xa and anti-IIa activities. Heparin Red is a polycationic substance whose intrinsic fluorescence is quenched upon binding to heparin. As such, assays utilizing Heparin Red detect all heparin oligosaccharides in a sample: those that bind to AT and produce anti-Xa and anti-IIa activities, and those that do not.
Aims: Thus, the pharmacokinetic behavior of heparin (half-life, etc.) as determined using a Heparin Red assay may more closely reflect the absolute levels.
Methods: Primates were administered PMH (Medefil, Glendale Heights, IL) or BMH (KinMaster, Passo Fundo, Brazil) at a dose of 100 anti-Xa U/kg IV. Blood samples were collected prior to and at 15, 30, 60 and 120 minutes post-heparin administration. Heparin levels were assessed using a chromogenic anti-Xa assay and a Heparin Red assay relative to product-specific calibration curves. Pharmacokinetic parameters were assessed using a non-compartmental model.
Results: Peak levels of 1.45 ± 0.11 and 1.48 ± 0.08 U/ml were observed in PMH and BMH-treated primates, respectively. Using drug levels determined by anti-Xa assay, AUCs for bovine and porcine heparin treated animals were calculated to be 111.5 ± 11.0 and 108.8 ± 26.7 U*min*ml-1, respectively. By Heparin Red assay, peak circulating heparin levels were higher following BMH administration.
Conclusions: BMH, when administered at equivalent anti-Xa unit doses, produces comparable pharmacodynamic effects as PMH. Heparin Red assay may be useful for identifying the appropriate dose of protamine to completely neutralize BMH. Furthermore absolute quantitation of GAGs by Red Probe method in these studies provides a true pharmacodynamic effect of heparins accounting for the cumulative actions of both AT dependent and independent actions.
To cite this abstract in AMA style:Jeske W, Kouta A, Hoppensteadt D, Cera L, Duff R, Fareed J, Kraemer R. Absolute Measurement of Bovine and Porcine Heparin Red Assay Utilizing the Heparin Red Assay. Applications in the Study of Pharmacokinetics and Pharmacodynamics [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/absolute-measurement-of-bovine-and-porcine-heparin-red-assay-utilizing-the-heparin-red-assay-applications-in-the-study-of-pharmacokinetics-and-pharmacodynamics/. Accessed November 29, 2021.
« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/absolute-measurement-of-bovine-and-porcine-heparin-red-assay-utilizing-the-heparin-red-assay-applications-in-the-study-of-pharmacokinetics-and-pharmacodynamics/