Pharmacokinetic Profile of Atenolol Aspirinate

Montes-Gil, Ana C.; Zanfolin, Marcos; Okuyama, Cristina Eunice; Lilla, Sérgio; Alves, Delma Pegolo; Santagada, Vincenzo; Perissutti, Elisa; Lavecchia, Antonio; Fiorino, Ferdinando; Severino, Beatrice; Caliendo, Giuseppe; Priviero, Fernanda; Mendes, Gustavo Duarte; Donato, José L.; Nucci, Gilberto De

doi:10.1002/ardp.200700070

Cited by 3 publications

(2 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, aspirinate ester formation of α-aminoalcohol is rarely reported. N -Boc protected α-aminoalcohol could be aspirinated by treatment with DCC or polymer-supported CDI with aspirin [17]. To the best of our knowledge, there is only one precedent for the aspirination of an alcohol compound having a tertiary amino group at the α-position, in which aspirinic anhydride was used as a coupling reagent to yield the corresponding ester compound at a low yield (19%) [18].…”

Section: Introductionmentioning

confidence: 99%

Aspirination of α-Aminoalcohol (Sarpogrelate M1)

et al. 2016

View full text Add to dashboard Cite

Aspirination of α-aminoalcohol (sarpogrelate M1) has been performed under various general esterification conditions. In most cases, the desired aspirinate ester was obtained at a low yield with unexpected byproducts, the formation of which was mostly derived from the chemical properties of the tertiary α-amino group. After systematic analysis of those methods, the aspirinated sarpogrelate M1 was prepared using a two-step approach combining salicylate ester formation and acetylation.

show abstract

Section: Introductionmentioning

confidence: 99%

Aspirination of α-Aminoalcohol (Sarpogrelate M1)

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Previous studies on stability of atenolol ester prodrugs for the use in transdermal preparations have shown that these ester derivatives are much more stable than the corresponding alcohol, atenolol, when they are formulated in aqueous solutions [26, 27]. On the other hand, the only atenolol prodrug intended to be used for oral dosage form was atenolol aspirinate prodrug (aspirin); it is described for antihypertensive therapy to reduce cardiovascular death, stroke, and myocardial infarction (MI); however, recent studies reported that the coupling of atenolol with acetyl salicylic acid by means of an ester linkage did not produce any efficient pharmacological profile, neither in vitro nor in vivo [28].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, andIn VitroKinetics Study of Atenolol Prodrugs for the Use in Aqueous Formulations

Qtait

Dajani

Lafi

2014

The Scientific World Journal

View full text Add to dashboard Cite

Based on DFT, MP2, and the density functional from Truhlar group (hybrid GGA: MPW1k) calculations for an acid-catalyzed hydrolysis of nine Kirby's N-alkylmaleamic acids and two atenolol prodrugs were designed. The calculations demonstrated that the amide bond cleavage is due to intramolecular nucleophilic catalysis by the adjacent carboxylic acid group and the rate-limiting step is determined based on the nature of the amine leaving group. In addition, a linear correlation of the calculated and experimental rate values has drawn credible basis for designing atenolol prodrugs that are bitterless, are stable in neutral aqueous solutions, and have the potential to release the parent drug in a sustained release manner. For example, based on the calculated B3LYP/6-31 G (d,p) rates, the predicted t 1/2 (a time needed for 50% of the prodrug to be converted into drug) values for atenolol prodrugs ProD 1-ProD 2 at pH 2 were 65.3 hours (6.3 hours as calculated by GGA: MPW1K) and 11.8 minutes, respectively. In vitro kinetic study of atenolol prodrug ProD 1 demonstrated that the t 1/2 was largely affected by the pH of the medium. The determined t 1/2 values in 1N HCl, buffer pH 2, and buffer pH 5 were 2.53, 3.82, and 133 hours, respectively.

show abstract