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Differential Pharmacokinetics of Sulfaminoheparosans (SAHs) and Heparins In Vivo in Rats : Pharmacological Implications
Author(s) -
Maddineni Jyothi,
Cornelli Umberto,
Mai Marco,
Hoppensteadt Debra,
Fareed Jawed
Publication year - 2006
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.20.5.a1140-a
Subject(s) - pharmacology , in vivo , pharmacokinetics , heparin , anticoagulant , distribution (mathematics) , medicine , low molecular weight heparin , bioavailability , chemistry , biology , microbiology and biotechnology , mathematical analysis , mathematics
Background Bacterial (E.coli) polysaccharide (K5) derived SAHs exhibit comparable anticoagulant and antiprotease profile as heparins. The objective of this study is to determine the circulating plasma levels of two SAH fractions (Bio‐20 and bio‐6 kDa) with mean molecular weights of 20 kDa and 6 kDa in vivo in male Sprague‐Dawley rats. Method Bio‐20 kDa and bio‐6 kDa were administered intravenously (I.V), subcutaneously (S.C) and orally. The blood was drawn 3 hours post administration from S.C and oral groups and 5 minutes post administration from I.V group. Plasma levels of the agents were assessed using anti‐Xa and anti‐IIa methods. The results were compared to unfractionated heparin (UFH) and tinzaparin. Results The circulating levels of tinzaparin are significantly (p < 0.05) more than the bio‐20, bio‐6 kDa and UFH in I.V at 0.5 mg/kg, both in anti‐Xa and anti‐IIa assays. The plasma levels of bio‐20 kDa and bio‐6 kDa were almost same and UFH is comparably less available of all. In S.C administration, as determined in anti‐Xa assay, tinzaparin and bio‐6 kDa (10 mg/kg), have very high plasma concentrations when compared to UFH and bio‐20 kDa (5 mg/kg). Bio‐20 kDa has lowest availability subcutaneously. In anti‐IIa assay, tinzaparin has significantly (p < 0.05) higher availability of all the agents. Bio‐6 kDa has very less concentrations available in comparison to tinzaparin. UFH and bio‐20 kDa exhibited almost similar circulating levels. There are no circulating plasma levels of both the bio‐20 kDa and bio‐6 kDa available following oral administration. Conclusions These studies clearly demonstrate that independent of the in virto anti‐Xa/IIa activities, the SAHs and heparins exhibit differential assay dependent bioavailability.