Low molecular weight protamine (LMWP) as nontoxic heparin/low molecular weight heparin antidote (II): In vitro evaluation of efficacy and toxicity
Journal Title: The AAPS Journal - Year 2001, Vol 3, Issue 3
Abstract
Patients undergoing anticoagulation with heparin or low molecular weight heparin (LMWH) require a superior antidote that possesses more selective biological actions and a better safety profile than protamine. We had previously developed 2 low molecular weight protamine (LMWP) fractions (TDSP4 and TDSP5) from thermolysin-digested protamine as potential nontoxie, heparin-neutralizing agents. In this, the second article in this series, studies focused on in vitro evaluation of heparin/LMWH-neutralizing efficacy and putative toxicity. These LMWP fractions, particularly TDSP5, were effective and fully capable of neutralizing a broad spectrum of heparin-induced anticoagulant activities (ie, aPTT, anti-Xa, and anti-IIa activities). Additionally, these LMWP fractions could neutralize the activities of commercial LMWH. As assessed by the anti-Xa assay, TDSP5 was as effective as, although less potent than, protamine in reversing the activity of Mono-Embolex (molecular weight 5000–7000) and 2 other different sizes (molecular weight of 3000 and 5000 d) of LMWH preparations. Furthermore, compared with protamine, TDSP5 exhibited a much-reduced toxicity and thus an improved safety profile, as reflected by its reduced ability to activate the complement system and cross-react with the antiprotamine antibodies, which are 2 primary indices of protamine toxicity.
Authors and Affiliations
Li-Chien Chang, Jun Feng Liang, Hsiao-Feng Lee, Lai Ming Lee, Victor C Yang
Keywords
Related Articles
- EP ID EP682057
- DOI 10.1208/ps030318
- Views 103
- Downloads 0
Prediction of Deleterious Non-synonymous Single-Nucleotide Polymorphisms of Human Uridine Diphosphate Glucuronosyltransferase Genes
The online version of this article (doi:10.1208/s12248-009-9126-z) contains supplementary material, which is available to authorized users.
The Gender of Cell Lines Matters When Screening for Novel Anti-Cancer Drugs
Current reports indicated that the gender origin of cells is important in all facets of experimental biology. To explore this matter using an anticancer high throughput screening platform, seven male- and seven female-de...
Absorption, Distribution, Metabolism, and Excretion (ADME) Studies of Biotherapeutics for Autoimmune and Inflammatory Conditions
Biotherapeutics are becoming an increasingly common drug class used to treat autoimmune and other inflammatory conditions. Optimization of absorption, distribution, metabolism, and excretion (ADME) profiles of biotherape...
Tissue Distribution Studies of Protein Therapeutics Using Molecular Probes: Molecular Imaging
Molecular imaging techniques for protein therapeutics rely on reporter labels, especially radionuclides or sometimes near-infrared fluorescent moieties, which must be introduced with minimal perturbation of the protein&#...
Genetic Polymorphisms of Metabolic Enzymes and the Pharmacokinetics of Indapamide in Taiwanese Subjects
To understand the genetic makeup and impact on pharmacokinetics (PK) in the Taiwanese population, we analyzed the pharmacogenetic (PG) profile and demonstrated its effects on enzyme metabolism using indapamide as an exam...