Improved Pharmacokinetics of AMG 517 Through Co-Crystallization Part 1: Comparison of Two Acids With Corresponding Amide Co-crystals
| Autor: | Matthew Peterson, Adria E. Colletti, Eric J. Munson, Mary K. Stanton, Y.-H. Kiang, John Roberts, Mary C. Wells, Meghan Langley, Ron C. Kelly |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Stereochemistry Carboxylic acid TRPV Cation Channels Pharmaceutical Science Crystallography X-Ray Cinnamic acid Rats Sprague-Dawley chemistry.chemical_compound Pharmacokinetics Amide Animals Benzothiazoles Benzamide Dissolution Benzoic acid chemistry.chemical_classification Free base Benzoic Acid Rats Pyrimidines Solubility chemistry Cinnamates Benzamides Crystallization Nuclear chemistry |
| Zdroj: | Journal of Pharmaceutical Sciences. 99:3769-3778 |
| ISSN: | 0022-3549 |
| Popis: | The dissolution and pharmacokinetics (PK) of two carboxylic acid co-crystals (cinnamic acid and benzoic acid) with the corresponding amide co-crystals (cinnamamide and benzamide) of AMG 517 were investigated. Powder and intrinsic dissolution studies were performed in fasted simulated intestinal fluid (FaSIF). Suspension formulations in 1% polyvinylpyrrolidone K25 in water were administered orally at 100 mg/kg to rats. The four co-crystals were found to have faster intrinsic and powder dissolution rates in FaSIF than the free base. This correlated with a 2.4- to 7.1-fold increase in the area under the concentration-time curve in rat PK investigations. When contrasting the acid to its corresponding amide co-crystal, cinnamamide shows improvement over cinnamic acid, while benzamide and benzoic acid perform similarly. |
| Databáze: | OpenAIRE |
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