Latenciação e formas avançadas de transporte de fármacos

Chin, Chung Man; Silva, Antonio Távora de Albuquerque; Castro, Lúcia Fioravanti; Güido, Rafael Victório Carvalho; Nassute, Jose Carlos; Ferreira, Elizabeth Igne

doi:10.1590/s1516-93322005000200004

Cited by 29 publications

(41 citation statements)

References 75 publications

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“…1 Since then, prodrugs have been highly explored to overcome several biologic barriers in drug delivery such as absorption, distribution and enzymatic metabolism. 2 In drug development programs, difficulties such as low solubility, premature degradation, short half-life and other pharmacokinetic and pharmacodynamic parameters can also be tackled with a prodrug approach. 3 However, in order to become a prodrug candidate, a molecule must present some features such as biologic inactivity, absence of toxicity, simple synthetic route, a biolabile drug-carrier conjugate and ensure effective concentration of the drug in the target tissues.…”

Section: Introductionmentioning

confidence: 99%

Acetaminophen Prodrug: Microwave-Assisted Synthesis andin vitroMetabolism Evaluation by Mass Spectrometry

Murie¹,

Marques²,

Souza³

et al. 2016

Journal of the Brazilian Chemical Society

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Propacetamol is an acetaminophen prodrug of intravenous administration used to control fever and pain of perioperative period in multimodal analgesia therapy. After injection, it is completely converted by plasma esterases into N,N-diethylglycine and acetaminophen, its active metabolite whose mechanism of action is the inhibition of prostaglandin synthesis. Herein, we report an improved protocol for the synthesis of propacetamol hydrochloride that allows the isolation of the active pharmaceutical ingredient (API) with high purity and yield. In addition, the in vitro metabolism of propacetamol in a microssomal reaction was evaluated by ion trap tandem mass spectrometry.

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Section: Introductionmentioning

confidence: 99%

Acetaminophen Prodrug: Microwave-Assisted Synthesis andin vitroMetabolism Evaluation by Mass Spectrometry

Murie¹,

Marques²,

Souza³

et al. 2016

Journal of the Brazilian Chemical Society

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“…Regarding prodrug design strategy, or latentiation method, the main purpose is to modify physicochemical properties of drugs to reduce undesirable pharmacokinetic features, but maintaining drug's intrinsic activity. Thus, the drugs' physicochemical properties can be adjusted through a proper choice of carrier groups in order to increase oral absorption, for example (11,12).…”

Section: Introductionmentioning

confidence: 99%

To Be Drug or Prodrug: Structure-Property Exploratory Approach Regarding Oral Bioavailability

et al. 2014

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-Purpose. Prodrug design is a strategy that can be used to adjust physicochemical properties of drugs in order to overcome pharmacokinetic problems, such as poor oral bioavailability. However, Lipinski´s and Veber´s rules predict whether compounds will have absorption problems even before the design of prodrugs. In this context, our goal was to evaluate the molecular properties which most influenced the absorption process of prodrugs compared to its precursor through exploratory data analysis approach. Methods: A variety of prodrugs and respective precursors were randomly selected and classified by its' percentage of human intestinal absorption. Subsequently, different molecular properties were calculated and hierarchical cluster analysis (HCA) and principal components analysis (PCA) were carried out. Results: According to the findings, antiviral, anti-hypertensive, and antibiotic prodrugs exhibited higher absorption levels than their respective precursors. Also, some relevant descriptors (molecular weight, MW, routable bonds, rot_bonds, hydrogen bond acceptors, HBA_count and polar surface area, PSA), which are included in Lipinski´s and Veber´s rules, influenced the separation process between prodrugs and drugs. Furthermore, other molecular properties, such as polarizability (α) and molar refractivity (MR), were pointed out. Conclusion: Lipinski´s and Veber´s rules proved to be important to design an orally administered drug but other descriptors should be considered by medicinal chemists in the prodrug designing process.

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“…It is a temporarily inactive compound that, once inside the organism, needs to be metabolized to attain its active form (Bundgaard, 1985;Bundgaard, 1991;Chung et al, 2005;Liederer, Borchardt, 2006;Parise-Filho et al, 2007;Rautio et al, 2008;Silva et al, 2005;Stella, 2004;Wermuth, 2006).…”

Section: Introductionmentioning

confidence: 99%

Prodrugs available on the Brazilian pharmaceutical market and their corresponding bioactivation pathways

Parise-Filho

Polli

Barberato‐Filho

et al. 2010

Braz. J. Pharm. Sci.

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The aim of this paper was to emphasize the importance of prodrug design to therapy, by examining examples available on the Brazilian pharmaceutical market. The principles of prodrug design are briefly discussed herein. Examples of prodrugs from many important therapeutic classes are shown and their advantages relative to the drugs they are derived from are also discussed. Considering the importance of these therapeutic classes, from both therapy and economic standpoints, prodrug design is a very valuable aspect in the research of new drugs and for the pharmaceutical industry as a whole.Uniterms: Prodrug design. Molecular modification. Drug development.O objetivo do trabalho foi ressaltar a importância do planejamento de pró-fármacos para a terapia, por meio de exemplos disponíveis no mercado farmacêutico brasileiro. Os princípios da latenciação são sucintamente discutidos. Apresentam-se exemplos de pró-fármacos de muitas classes terapêuticas importantes e as vantagens relativas aos fármacos dos quais derivam são, também, discutidas. Considerando-se a importância dessas classes terapêuticas, tanto do aspecto terapêutico quanto do econômico, o planejamento de pró-fármacos representa aspecto de grande valor na busca de novos fármacos e na indústria farmacêutica como um todo.Uniterms: Pró-fármacos/planejamento Fármacos/latenciação. Modificação molecular. Fármacos/ desenvolvimento.

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Latenciação e formas avançadas de transporte de fármacos

Cited by 29 publications

References 75 publications

Acetaminophen Prodrug: Microwave-Assisted Synthesis andin vitroMetabolism Evaluation by Mass Spectrometry

Acetaminophen Prodrug: Microwave-Assisted Synthesis andin vitroMetabolism Evaluation by Mass Spectrometry

To Be Drug or Prodrug: Structure-Property Exploratory Approach Regarding Oral Bioavailability

Prodrugs available on the Brazilian pharmaceutical market and their corresponding bioactivation pathways

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