Pharmacokinetic profile of atenolol aspirinate

Ana C. Montes-Gil; Marcos Zanfolin; Cristina E. Okuyama; Sergio Lilla; Delma P. Alves; Vincenzo Santagada; Elisa Perissutti; Antonio Lavecchia; Ferdinando Fiorino; Beatrice Severino; Giuseppe Caliendo; Fernanda Priviero; Gustavo D. Mendes; Jose L. Donato; Gilberto De Nucci

doi:10.1002/ardp.200700070

Pharmacokinetic profile of atenolol aspirinate

Ana C. Montes-Gil
, Marcos Zanfolin
, Cristina E. Okuyama
, Sergio Lilla
, Delma P. Alves
, Vincenzo Santagada
, Elisa Perissutti
, Antonio Lavecchia
, Ferdinando Fiorino
, Beatrice Severino
, Giuseppe Caliendo
, Fernanda Priviero
, Gustavo D. Mendes
, Jose L. Donato
, Gilberto De Nucci

Physiology

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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.

Original language	English (US)
Pages (from-to)	445-455
Number of pages	11
Journal	Archiv der Pharmazie
Volume	340
Issue number	9
DOIs	https://doi.org/10.1002/ardp.200700070
State	Published - Sep 2007

Keywords

Antihypertensive therapy
Atenolol
Microwave synthesis
Pharmacokinetics
Prodrug

ASJC Scopus subject areas

Pharmaceutical Science
Drug Discovery

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10.1002/ardp.200700070

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@article{c35a1d5b425e40019b51972937d7c499,

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{\textregistered}) was connected to atenolol by an ester linkage. Atenolol aspirinate was stable towards aqueous hydrolysis but rapidly hydrolyzed in plasma (t1/2 = 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.",

keywords = "Antihypertensive therapy, Atenolol, Microwave synthesis, Pharmacokinetics, Prodrug",

author = "Montes-Gil, \{Ana C.\} and Marcos Zanfolin and Okuyama, \{Cristina E.\} and Sergio Lilla and Alves, \{Delma P.\} and Vincenzo Santagada and Elisa Perissutti and Antonio Lavecchia and Ferdinando Fiorino and Beatrice Severino and Giuseppe Caliendo and Fernanda Priviero and Mendes, \{Gustavo D.\} and Donato, \{Jose L.\} and \{De Nucci\}, Gilberto",

note = "Funding Information: The work described in this paper was in part, supported as part of the Esprit Me{"}sto project, the British Aerospace Dependable Computing Systems Centre and the BAe Centre of Excellence in Cockpit Automation Research. I am also indebted to John McCarthy and Pat Healey for the article that inspired some of our thinking in this paper (Healey \& McCarthy, 1997). Thanks are due to the anonymous referees who were patient enough to read a rough version of this paper and make highly constructive comments.",

year = "2007",

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doi = "10.1002/ardp.200700070",

language = "English (US)",

volume = "340",

pages = "445--455",

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T1 - Pharmacokinetic profile of atenolol aspirinate

AU - Montes-Gil, Ana C.

AU - Zanfolin, Marcos

AU - Okuyama, Cristina E.

AU - Lilla, Sergio

AU - Alves, Delma P.

AU - Santagada, Vincenzo

AU - Perissutti, Elisa

AU - Lavecchia, Antonio

AU - Fiorino, Ferdinando

AU - Severino, Beatrice

AU - Caliendo, Giuseppe

AU - Priviero, Fernanda

AU - Mendes, Gustavo D.

AU - Donato, Jose L.

AU - De Nucci, Gilberto

N1 - Funding Information: The work described in this paper was in part, supported as part of the Esprit Me"sto project, the British Aerospace Dependable Computing Systems Centre and the BAe Centre of Excellence in Cockpit Automation Research. I am also indebted to John McCarthy and Pat Healey for the article that inspired some of our thinking in this paper (Healey & McCarthy, 1997). Thanks are due to the anonymous referees who were patient enough to read a rough version of this paper and make highly constructive comments.

PY - 2007/9

Y1 - 2007/9

N2 - 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 (t1/2 = 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.

AB - 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 (t1/2 = 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.

KW - Antihypertensive therapy

KW - Atenolol

KW - Microwave synthesis

KW - Pharmacokinetics

KW - Prodrug

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DO - 10.1002/ardp.200700070

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AN - SCOPUS:34748819542

SN - 0365-6233

VL - 340

SP - 445

EP - 455

JO - Archiv der Pharmazie

JF - Archiv der Pharmazie

IS - 9

ER -

Pharmacokinetic profile of atenolol aspirinate

Abstract

Keywords

ASJC Scopus subject areas

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