(537.17) USP Potency Adjusted Bovine Mucosal Heparins are Comparable to Porcine Mucosal Heparin and May be Interchangeable for Anticoagulation

Poster Board Number: B93

Guy Olson (Loyola University Medical Center), Ahmed Kouta (Loyola University Medical Center), Nausheen Baig (Loyola University Medical Center), Walter Jeske (Loyola University Medical Center), Debra Hoppensteadt (Loyola University Medical Center), Massimo Iacobelli (Loyola University Medical Center), Omer Iqbal (Loyola University Medical Center), Mamdouh Bakhos (Loyola University Medical Center), Lee Cera (Loyola University Medical Center), Vinod Bansal (Loyola University Medical Center), Jawed Fareed (Loyola University Medical Center)

Introduction: Most of the heparins used clinically are derived from porcine intestinal mucosa. In contrast to the porcine mucosal heparin (PMH), the active pharmaceutical ingredient (API) of bovine mucosal heparin (BMH) exhibit a somewhat weaker USP potency as cross-referenced against PMH. We hypothesized that at equivalent potencies as adjusted by using the USP reference, the BMH may exhibit comparable effects.

Materials amp;

Methods: Molecular weight profile and in vitro anticoagulant and antiprotease assays were used to compare the BMH with PMH. USP potency was measured in the amidolytic assays. Potency adjustments in reference to USP standard were made by weight basis. Potency adjusted BMH and PMH were injected at identical dosages (50 U/kg and 100 U/kg) to groups of human primates (n=4) via intravenous route and blood samples were collected for a 6 hour period of time.

Results: BMH exhibited higher molecular weight profiles compared to PMH as determined by size exclusion chromatography {BMH (Mw) 18.6 ± 0.5 kDa and PMH 15.4 ± 0.4 kDa}. BMH showed a potency of 130 U/mg whereas PMH showed a potency of 190 U/mg. When the BMH was compared at a potency adjusted concentration with PMH, it showed identical calibration curves in the aPTT and anti-protease assays. Mean t1/2 ranged from 54 ± 11 min amp; to 71 ± 18 min for PMH amp; BMH respectively (p=gt;0.05). Mean AUC values based on anti-Xa or anti-IIa activities were comparable for both heparins. Mean Vd (~60 ml/kg) and Cl (~0.75 ml/kg/min) were also comparable for both heparins.

Conclusion: Potency adjusted based dosing results in comparable anticoagulants and pharmacokinetic profiles for BMH and PMH. Therefore, such dosing may provide uniform levels of anticoagulation for the parenteral indications for heparins. These observations suggest that potency equated BMH and PMH produced comparable anticoagulant effects and may be interchangeable.