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Pharmacokinetics and Pharmacodynamics of Oral Heparin Solid Dosage Form in Healthy Human Subjects
Author(s) -
Mousa Shaker A.,
Zhang Fuming,
Aljada Ahmad,
Chaturvedi Seema,
Takieddin Majde,
Zhang Haifeng,
Chi Lianli,
Castelli M. Cristina,
Friedman Kristen,
Goldberg Michae M.,
Linhardt Rober J.
Publication year - 2007
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270007307242
Subject(s) - heparin , pharmacokinetics , partial thromboplastin time , pharmacodynamics , chemistry , pharmacology , oral administration , crossover study , chromatography , medicine , biochemistry , platelet , alternative medicine , pathology , placebo
The present investigation determined the molecular structure and the pharmacokinetic and pharmacodynamic profiles of oral unfractionated heparin containing oral absorption enhancer sodium N‐[8‐(2‐hydroxybenzoyl) amino]caprylate, salcaprozate sodium (SNAC) and assessed the safety and tolerability of the orally dosed heparin solid dosage form versus other routes. Sixteen healthy men were included in this single‐dose, 3‐way crossover, randomized, open‐label study. Disaccharide compositional analysis was performed using capillary high‐performance liquid chromatography with electrospray ionization mass spectrometry detection. The pharmacodynamics of heparin were obtained from analysis of plasma anti–factor Xa, anti–factor IIa, activated partial thromboplastin time, and total tissue factor pathway inhibitor data. The molecular weight properties and the disaccharide composition of orally administered unfractionated heparin/SNAC and parenterally administered unfractionated heparin are identical and consistent with the starting pharmaceutical standard heparin. Furthermore, the anti–factor Xa/anti–factor IIa ratio achieved is of approximately 1:1. This is the first true pharmacokinetic study to measure the chemical compositions of heparin administered by different routes.