Pharmacokinetics and pharmacodynamics of oral heparin solid dosage form in healthy human subjects

• Published in: Journal of clinical pharmacology Vol. 47; no. 12; p. 1508
• Main Authors: Mousa, Shaker A, Zhang, Fuming, Aljada, Ahmad, Chaturvedi, Seema, Takieddin, Majde, Zhang, Haifeng, Chi, Lianli, Castelli, M Cristina, Friedman, Kristen, Goldberg, Michael M, Linhardt, Robert J
• Format: Journal Article
• Language: English
• Published: England 01.12.2007
• Subjects: Administration, Oral; Adult; Caprylates - chemistry; Capsules; Chromatography, High Pressure Liquid; Cross-Over Studies; Gelatin - chemistry; Heparin, Low-Molecular-Weight - administration & dosage; Heparin, Low-Molecular-Weight - chemistry; Heparin, Low-Molecular-Weight - pharmacokinetics; Humans; Injections, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Spectrometry, Mass, Electrospray Ionization
• ISSN: 0091-2700
• DOI: 10.1177/0091270007307242

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.