Pharmacokinetic profile of atenolol aspirinate.
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.
Montes-Gil
Ana C
AC
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil.
Zanfolin
Marcos
M
Okuyama
Cristina E
CE
Lilla
Sergio
S
Alves
Delma P
DP
Santagada
Vincenzo
V
Perissutti
Elisa
E
Lavecchia
Antonio
A
Fiorino
Ferdinando
F
Severino
Beatrice
B
Caliendo
Giuseppe
G
Priviero
Fernanda B M
FB
Mendes
Gustavo D
GD
Donato
Jose L
JL
de  Nucci
Gilberto
G
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
D000959:Antihypertensive Agents; D011355:Prodrugs; D001262:Atenolol; D001241:Aspirin