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Comparative Pharmacokinetic Profile of Three Batches of Ovine Enoxaparin and One Batch of Branded Enoxaparin
Author(s) -
Rangnekar Varun,
Jeske Walter,
Yao Yiming,
Kouta Ahmed,
Hoppensteadt Debra,
Duff Rick,
Fareed Jawed
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb603
Subject(s) - low molecular weight heparin , pharmacokinetics , heparin , pharmacology , anticoagulant , chemistry , distribution (mathematics) , tissue factor pathway inhibitor , enoxaparin sodium , potency , medicine , coagulation , in vitro , surgery , biochemistry , tissue factor , mathematical analysis , mathematics
Background Heparins can be derived from tissues of a variety of different species. Although current pharmaceutical grade heparin is derived almost exclusively from porcine intestinal mucosa, there is interest within the FDA for diversifying the sourcing of heparin in the US to protect against supply shortages and economically motivated adulteration as was seen in 2008. Because sheep‐derived (ovine) heparin is structurally similar to porcine heparin, it is expected that low molecular weight heparin (LMWH) derived from ovine‐heparin will be comparable to porcine‐derived LMWH. This study will compared the pharmacokinetic behavior of ovine LMWH with that of enoxaparin in non‐human primates. Materials and Methods Enoxaparin (Lovenox, Sanofi‐Aventis, Bridgewater, NJ) and three batches of ovine LMWH produced by benzylaztion/alkaline hydrolysis (Suzhou Ronnsi Pharma, Suzhou, China) were used in this study. Following anesthesia, a baseline blood sample was collected from non‐human primates ( Macaca mulatta ; n=4/LMWH). LMWH was administered subcutaneously (SC) at a dose of 1 mg/kg. Additional blood samples were collected at 2, 4 and 6 hours post‐administration. Circulating drug concentrations determined using anti‐Xa and anti‐thrombin assays were used to calculate pharmacokinetic parameters such as half‐life, area under the curve, systemic clearance and volume of distribution using the PKSolver add‐in for Microsoft Excel. Tissue factor pathway inhibitor (TFPI) levels were measured by ELISA. Results In vitro studies demonstrated that the ovine LMWHs met pharmacopoeial requirements for enoxaparin in terms of potency and molecular weight distribution. In the samples collected at 2, 4, and 6 hours, comparable levels of branded enoxaparin and the three batches of ovine enoxaparin were observed using both anti‐Xa and anti‐thrombin assays, with the concentration vs. time curves being nearly superimposable. Consistent with the similarity observed with the plasma drug concentrations, no significant differences were observed between pharmacokinetic parameters calculated for branded enoxaparin and ovine LMWH. TFPI levels returned to baseline levels by 6 hours in ovine LMWH‐treated animals, but remained slightly elevated in animals treated with branded enoxaparin. Discussion At a 1 mg/kg SC dosage, three ovine enoxaparin preparations produced comparable anti‐Xa and anti‐IIa effects which were similar to the ones observed with branded enoxaparin. The PK parameters calculated based on this data were also comparable for both groups. It is concluded that the SC pharmacokinetics of the three batches of ovine enoxaparin were not only comparable between batched, but were also similar to the branded product. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .