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Your search keyword '"G., DE NUCCIA"' showing total 2 results
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2 results on '"G., DE NUCCIA"'

1. Pharmacokinetic profile of atenolol aspirinate

Author

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

2. Pharmacokinetics of dihydroergocristine and its major metabolite 8'-hydroxy-dihydroergocristine in human plasma

Author

Hilton O Dos Santos, Elisa Perissutti, Giovanni Carvalho Guzzo, Anna Aiello, Beatriz Bicalho, Vicenzo Santagada, Gilberto De Nucci, Giuseppe Caliendo, Sergio Lilla, Paolo Luciano, Alberto dos Santos Pereira, Gustavo D. Mendes, B., Bicalho, G. C., Guzzo, S., Lilla, H. O., DOS SANTOS, G. D., Mende, Caliendo, Giuseppe, Perissutti, Elisa, Aiello, Anna, Luciano, Paolo, Santagada, Vincenzo, A. S., Pereira, and G., DE NUCCIA

Subjects
Male, Metabolite, Vasodilator Agents, Clinical Biochemistry, Dihydroergocristine, Mass Spectrometry, Rats, Sprague-Dawley, chemistry.chemical_compound, Pharmacokinetics, medicine, Animals, Humans, Chromatography, High Pressure Liquid, Pharmacology, Chromatography, Molecular mass, Chemistry, Substrate (chemistry), Half-life, Reproducibility of Results, Rats, Human plasma, Area Under Curve, Microsome, Hepatocytes, Microsomes, Liver, Cattle, medicine.drug, Half-Life
Abstract

Dihydroergocristine (DHEC) is a semi-synthetic drug mainly used for age-related cognitive impairment. In this study, its major metabolite 8'-hydroxy-dihydroergocristine (8'-OH-DHEC) was produced in incubates of a bovine liver preparation using dihydroergocristine mesylate (DHECM) as substrate. Purification was achieved by flash silica gel column and reverse phase liquid chromatographies, and identification was based on accurate molecular mass measurements, mass fragmentation spectra and NMR ((1)H/(13)C) chemical shifts. By using the substance produced in vitro, a fast, sensitive, specific and robust LC/MS/MS method for the simultaneous determination of DHEC and its major metabolite in human plasma was developed and validated. Bromocriptine was used as internal standard and limits of quantification for DHEC and 8'-OH-DHEC were 10 pg/ml and 20 pg/ml, respectively. Pharmacokinetic parameters were investigated on 12 male healthy volunteers to whom a single dose of 18 mg DHECM was administered in tablets (Iskevert). The peak of DHEC was 0.28 +/- 0.22 microg/l, the t(max) 0.46 +/- 0.26 h, the AUC(last) 0.39 +/- 0.41 microg/l.h and the terminal elimination half-life 3.50 +/- 2.27 h. The peak of 8'-OH-DHEC was 5.63 +/- 3.34 microg/l, the t(max) 1.04 +/- 0.66 h, the AUC(last) 13.36 +/- 5.82 microg/l.h and the terminal elimination half-life 3.90 +/- 1.07 h. Dosing of 18 mg DHECM was well tolerated, causing no adverse events.

Published
2005

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