Prodrugs as drug delivery systems. 68. Chemical and plasma-catalyzed hydrolysis of various esters of benzoic acid: a reference system for designing prodrug esters of carboxylic acid agents

Nielsen, Niels Mørk; Bundgaard, Hans

doi:10.1016/0378-5173(87)90200-6

Cited by 44 publications

(14 citation statements)

References 26 publications

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“…O diferente comportamento deste composto foi atribuído à presença da carga negativa na sua estrutura ao pH fisiológico -pois ésteres contendo cargas negativas próximas da ligação éster são freqüentemente pobres substratos para esterases (Nielsen, Bundgaard, 1987) -juntamente com o maior impedimento estérico na cadeia lateral do sistema transportador.…”

Section: O íOn Carboxilato Como Agente Nucleofílicounclassified

Ciclização intramolecular: uma estratégia promissora no desenvolvimento de pró-fármacos

Santos¹

2008

Rev. Bras. Cienc. Farm.

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Muitos fármacos estão associados a vários efeitos adversos INTRODUÇÃOMuitos fármacos que apresentam elevada atividade contra várias doenças estão relacionados com problemas que os tornam limitados ou inviáveis como sistemas terapêuticos eficazes (Guettari et al., 1997;Song et al., 2005). Solubilidade, estabilidade, absorção, distribuição, toxicidade e biodisponibilidade são aspectos fundamentais a serem levados em consideração quando da administração de um fármaco (Lynx et al., 2006;Otto, 2004;Vennerstrom et al., 1999;Thomsen et al., 2004). Um exemplo comum de fármacos que estão relacionados com vários problemas de natureza terapêutica é encontrado nos análogos das purinas e pirimidinas. Os fármacos contidos nestas classes de compostos são conhecidos pelas suas baixas biodisponibilidades orais (Thomsen et al., 2003). O aciclovir, por exemplo, é um análogo purínico que apresenta uma biodisponibilidade oral de cerca de 20% em adultos (Steingrimsdottir et al., 2000). Já a fluorouracila, que é um análogo pirimidínico, apresenta uma biodisponibilidade oral que varia entre indivíduos numa escala de 0-80% (Guo et al., 1995;Heyden et al., 1999;Zinutti et al., 1998). Além da reduzida biodisponibilidade destes fármacos, problemas associados à elevada toxicidade e baixa solubilidade, tanto em meio aquoso quanto em meio lipofílico, são um verdadeiro entrave nas suas aplicações terapêuticas (De Vrueh et al., 1998;Han et al., 1998;Zambonin et al., 1998).Um medicamento acabado é fruto de décadas de pesquisa química, farmacêutica e clínica. No entanto, muitas vezes subsistem problemas como os anteriormente menci-

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Section: O íOn Carboxilato Como Agente Nucleofílicounclassified

Ciclização intramolecular: uma estratégia promissora no desenvolvimento de pró-fármacos

Santos¹

2008

Rev. Bras. Cienc. Farm.

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“…The butyl ester was the least resistant (t½ 24 minutes), while the ethyl ester was the most resistant to hydrolysis (t½ 210 minutes). The plasma half-lives were 19 and 15 minutes for phenyl benzoate and benzyl benzoate, respectively (Nielsen and Bundgaard, 1987). …”

Section: Supporting Substances From Subgroupmentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 20, Revision 3(FGE.20Rev3): Benzyl alcohols, benzaldehydes, a related acetal, benzoic acids, and related esters from chemical groups 23 and 30

Publication¹

2011

EFS2

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The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to consider in this revision 3 of Flavouring Group Evaluation 20, the SCF Opinion on benzoic acid. Furthermore information on stereoisomeric composition for two substances and new information to support the re-allocation of the structural class for the candidate substance piperonyl alcohol ] has been submitted. The 41 flavouring substances in Flavouring Group Evaluation 20 were evaluated using the Procedure in Commission Regulation (EC) No 1565/2000. None of the substances were considered to have genotoxic potential. The substances were evaluated through a stepwise approach (the Procedure) that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that all the substances do not give rise to safety concerns at their levels of dietary intake, estimated on the basis of the MSDI approach. Twenty-two of the flavouring substances in the present group have been reported to occur naturally in a wide range of food items.In its evaluation, the Panel as a default used the "Maximised Survey-derived Daily Intake" (MSDI) approach to estimate the per capita intakes of the flavouring substances in Europe. However, when the Panel examined the information provided by the European Flavour Industry on the use levels in various foods, it appeared obvious that the MSDI approach in a number of cases would grossly underestimate the intake by regular consumers of products flavoured at the use level reported by the industry, especially in those cases where the annual production values were reported to be small. In consequence, the Panel had reservations about the data on use and use levels provided and the intake estimates obtained by the MSDI approach.In the absence of more precise information that would enable the Panel to make a more realistic estimate of the intakes of the flavouring substances, the Panel has decided also to perform an estimate of the daily intakes per person using a "modified Theoretical Added Maximum Daily Intake" (mTAMDI) approach based on the normal use levels reported by Industry. In those cases where the mTAMDI approach indicated that the intake of a flavouring substance might exceed its corresponding threshold of concern, the Panel decided not to carry out a formal safety assessment using the Procedure. In these cases the Panel requires more precise data on use and use levels.According to the default MSDI approach, the 37 flavouring substances allocated to structural class I have intakes in Europe from 0.001 to 610 microgram/capita/day, which are below the threshold of concern value for structural class I (1800 microgram/person/day). The four substances in structural class II 05.066, 05.221 and 06.104] have estimated intakes of 0.011, 1.2, 0.61 and 100 microgram/capita/day, respectively. These intakes are below the threshold values of 540 ...

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Section: Supporting Substances From Subgroupmentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 20, Revision 2 (FGE.20Rev2): Benzyl alcohols, benzaldehydes, a related acetal, benzoic acids, and related esters from chemical groups 23 and 30

Flavourings¹

2010

EFSA Journal

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Prodrugs as drug delivery systems. 68. Chemical and plasma-catalyzed hydrolysis of various esters of benzoic acid: a reference system for designing prodrug esters of carboxylic acid agents

Cited by 44 publications

References 26 publications

Ciclização intramolecular: uma estratégia promissora no desenvolvimento de pró-fármacos

Ciclização intramolecular: uma estratégia promissora no desenvolvimento de pró-fármacos

Scientific Opinion on Flavouring Group Evaluation 20, Revision 3(FGE.20Rev3): Benzyl alcohols, benzaldehydes, a related acetal, benzoic acids, and related esters from chemical groups 23 and 30

Scientific Opinion on Flavouring Group Evaluation 20, Revision 2 (FGE.20Rev2): Benzyl alcohols, benzaldehydes, a related acetal, benzoic acids, and related esters from chemical groups 23 and 30

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