Pharmacokinetic and Pharmacodynamic Profiles of Potency‐Adjusted Doses of Bovine, Ovine and Porcine Heparin are Comparable in a Primates Model
Authors: Kouta Ahmed , Jeske Walter , Duff Rick , Hoppensteadt Debra , Cera Lee , Azarafrooz Farshid , Cornelli Umberto , Fareed Jawed 
Published: June 2021

BackgroundUnfractionated heparin remains to be the only parenteral anticoagulant for various indications. Currently heparin is mainly derived from porcine mucosal heparin tissues. The USFDA and other regulatory agencies have considered resourcing heparin from alternate sources. Currently sheep (ovine) and cow (bovine) mucosal heparins are being developed for clinical use. The purpose of this study was to compare commercially available porcine heparin with the heparins obtained from bovine and ovine mucosal sources.Materials and MethodsBovine, ovine and porcine heparins were obtained from various commercial sources. Potencies of each heparin were determined by an amidolytic anti‐Xa assay in relation to the USP heparin standard. Individual groups of primates (n=4) were administered 100 anti‐Xa U/kg dosage of bovine, ovine or porcine heparin via intravenous route. Blood samples were collected at baseline, 15, 30, 60 and 120 minutes post‐administration. Anti‐Xa and anti‐IIa activities were measured to determine circulating heparin concentrations using commercially available USP compliant kits (Aniara Diagnostica, West Chester, OH). These drug concentrations were used to determine pharmacokinetic parameters such as area under the curve (AUC), half‐life (t1/2), clearance (Cl) and volume of distribution (Vd) using the PKSolver add‐in for Excel. The tissue factor pathway inhibitor (TFPI) levels were measured at 15 minutes.ResultsThe concentration vs. time curves for the three heparins were almost superimposable. Peak drug levels of approximately 1.5 and 1.4 U/mL were measured using anti‐Xa and anti‐IIa assays, respectively. After 2 hours, circulating drug levels were decreased to approximately 0.4 U/mL for all heparins. Pharmacokinetic parameters calculated from plasma concentration‐time curves indicated that all three heparins behaved similarly. Mean half‐life based on anti‐Xa activity ranged from 44 ± 13 min for ovine heparin to 71 ± 18 min for bovine heparin. Slightly longer half‐lives were observed using plasma concentrations determined using anti‐IIa activity. Mean AUC values based on anti‐Xa or anti‐IIa activities were comparable for all heparins. Mean Vd (~60 ml/kg) and Cl (~0.75 ml/kg/min) were also comparable for all heparins. The TFPI levels were similar for the porcine and ovine heparin whereas the bovine heparin exhibited lower levels.ConclusionAt a gravimetric level the bovine heparin exhibits a lower anticoagulant potency (140 U/mg) than ovine or porcine heparins (200 U/mg). USP cross‐referenced anti‐Xa potency adjusted based dosing results in comparable pharmacokinetic profiles for all three heparins. Therefore such dosing may provide uniform levels of anticoagulation for the parenteral indications for heparins. These observations warrant clinical validations in the specific indications.Support or Funding InformationNone.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.