title: Pharmacokinetic profile of atenolol aspirinate.
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.
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Montes-Gil
authors.forename: Marcos
authors.initials: M
authors.lastname: Zanfolin
authors.forename: Cristina E
authors.initials: CE
authors.lastname: Okuyama
authors.forename: Sergio
authors.initials: S
authors.lastname: Lilla
authors.forename: Delma P
authors.initials: DP
authors.lastname: Alves
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Santagada
authors.forename: Elisa
authors.initials: E
authors.lastname: Perissutti
authors.forename: Antonio
authors.initials: A
authors.lastname: Lavecchia
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Fiorino
authors.forename: Beatrice
authors.initials: B
authors.lastname: Severino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Caliendo
authors.forename: Fernanda B M
authors.initials: FB
authors.lastname: Priviero
authors.forename: Gustavo D
authors.initials: GD
authors.lastname: Mendes
authors.forename: Jose L
authors.initials: JL
authors.lastname: Donato
authors.forename: Gilberto
authors.initials: G
authors.lastname: de  Nucci
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001241:Aspirin / Q000737:chemistry*; D001262:Atenolol / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D005753:Gastric Mucosa / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D008872:Microwaves; D008958:Models, Molecular; D009152:Mutagenicity Tests; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D000959:Antihypertensive Agents; D011355:Prodrugs; D001262:Atenolol; D001241:Aspirin