1. Pharmacokinetic profile of atenolol aspirinate
- Author
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José L. Donato, Beatrice Severino, Giuseppe Caliendo, Fernanda B.M. Priviero, Elisa Perissutti, Ferdinando Fiorino, Gilberto De Nucci, Ana C. Montes-Gil, Sergio Lilla, Antonio Lavecchia, Marcos Zanfolin, Vincenzo Santagada, Delma Pegolo Alves, Cristina E. Okuyama, Gustavo D. Mendes, A. C., MONTES GIL, M., Zanfolin, C. E., Okuyama, S., Lilla, D. P., Alve, Santagada, Vincenzo, Perissutti, Elisa, Lavecchia, Antonio, Fiorino, Ferdinando, Severino, Beatrice, Caliendo, Giuseppe, F. B. M., Priviero, G. D., Mende, J. L., Donato, and G., DE NUCCIA
- Subjects
Models, Molecular ,Pharmaceutical Science ,Hydrolysis ,chemistry.chemical_compound ,Pharmacokinetics ,Drug Discovery ,medicine ,Organic chemistry ,Animals ,Humans ,Prodrugs ,cardiovascular diseases ,pharmacokinetic studie ,Microwaves ,Antihypertensive Agents ,Aqueous solution ,Chromatography ,Aspirin ,Chemistry ,molecular modeling ,Mutagenicity Tests ,Prodrug ,Atenolol ,microwave sinthesi ,Gastric Mucosa ,Area Under Curve ,Salicylic acid ,Derivative (chemistry) ,circulatory and respiratory physiology ,medicine.drug ,Half-Life - Abstract
We report microwave-assisted synthetic routes, the pharmacokinetic profile along with results from ulcerogenicity and mutagenicity studies of atenolol aspirinate, and an already described derivative, in which acetyl salicylic acid (aspirin®) was connected to atenolol by an ester linkage. Atenolol aspirinate was stable towards aqueous hydrolysis but rapidly hydrolyzed in plasma (t 1/2 = 7.6 min). The results showed that the rapid and complete hydrolysis generates atenolol salicylate, which assumes a conformation stabilized by two intramolecular H-bonds, avoiding its further hydrolysis to salicylic acid and atenolol.
- Published
- 2007