Microbial Models for Drug Metabolism

Azerad, Robert

doi:10.1007/3-540-69791-8_8

Cited by 66 publications

(48 citation statements)

References 180 publications

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“…At present, apart from N-linked glucoside drug metabolites, only two O-linked glucosides of mycophenolic acid and morphine have been identified in humans [9,10] . In addition, glucuronide conjugation, which is a characteristic conjugation in humans, is rarely found in microorganisms, and only two examples of glucuronide conjugation have been reported [11] . Compared with the phase II reactions in humans, glucoside conjugation is the major metabolic pathway in microorganisms, and it is used extensively to study the detoxification of cytotoxins and carcinogens [12][13][14] .…”

Section: Discussionmentioning

confidence: 99%

Phase II metabolites of etofesalamide in filamentous fungi1

Huang

Sun

et al. 2005

Acta Pharmacologica Sinica

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Aim: To study phase II metabolites of etofesalamide in filamentous fungi. Methods: Seven fungi were screened to transform etofesalamide. The metabolites of etofesalamide were assayed using liquid chromatography coupled to mass spectrometry. The major metabolite was subject to enzymatic hydrolysis to confirm its structure. Results: Etofesalamide was converted into two phase II metabolites: glucoside and riboside conjugates. Glucoside conjugate was the major product with a yield greater than 90%; no phase I metabolites were detected. Conclusion: Glucoside and riboside conjugations of etofesalamide in filamentous fungi differ from the phase II metabolism of glucuronidation in mammals.

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Section: Discussionmentioning

confidence: 99%

Phase II metabolites of etofesalamide in filamentous fungi1

Huang

Sun

et al. 2005

Acta Pharmacologica Sinica

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“…This method uses eukaryotic microorganisms to produce metabolites similar to mammals, since microbial transformation systems could closely mimic most of the Phase I transformations of drugs observed in mammals, mainly those catalyzed by cytochrome P450 (Azerad, 1999).…”

Section: In Vitro and In Vivo Extrapolationmentioning

confidence: 99%

Twenty-six years of HIV science: an overview of anti-HIV drugs metabolism

Andrade

Freitas

Oliveira

2011

Braz. J. Pharm. Sci.

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From the identification of HIV as the agent causing AIDS, to the development of effective antiretroviral drugs, the scientific achievements in HIV research over the past twenty-six years have been formidable. Currently, there are twenty-five anti-HIV compounds which have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), cell entry inhibitors or fusion inhibitors (FIs), co-receptor inhibitors (CRIs), and integrase inhibitors (INIs). Metabolism by the host organism is one of the most important determinants of the pharmacokinetic profile of a drug. Formation of active or toxic metabolites will also have an impact on the pharmacological and toxicological outcomes. Therefore, it is widely recognized that metabolism studies of a new chemical entity need to be addressed early in the drug discovery process. This paper describes an overview of the metabolism of currently available anti-HIV drugs.Uniterms: AIDS/treatment. Drugs/anti-HIV. Drugs/metabolism. Antiretroviral drugs. Biotransformation.Da identificação do HIV como o agente causador da AIDS, ao desenvolvimento de fármacos antirretrovirais eficazes, os avanços científicos na pesquisa sobre o HIV nos últimos vinte e seis anos foram marcantes. Atualmente, existem vinte e cinco fármacos anti-HIV formalmente aprovados pelo FDA para utilização clínica no tratamento da AIDS. Estes compostos são divididos em seis classes: inibidores nucleosídeos de transcriptase reversa (INTR), inibidores nucleotídeos de transcriptase reversa (INtTR), inibidores não-nucleosídeos de transcriptase reversa (INNTR), inibidores de protease (IP), inibidores da entrada celular ou inibidores de fusão (IF), inibidores de co-receptores (ICR) e inibidores de integrase (INI). O metabolismo consiste em um dos maiores determinantes do perfil farmacocinético de um fármaco. A formação de metabólitos ativos ou tóxicos terá impacto nas respostas farmacológicas ou toxicológicas do fármaco. Portanto, é amplamente reconhecido que estudos do metabolismo de uma nova entidade química devem ser realizados durante as fases iniciais do processo de desenvolvimento de fármacos. Este artigo descreve uma abordagem do metabolismo dos fármacos anti-HIV atualmente disponíveis na terapêutica.Unitermos: AIDS/tratamento. Fármacos/anti-HIV. Fármacos/antirretrovirais. Fármacos/metabolismo. Biotransformação. INTRODUCTIONThe human immunodeficiency virus (HIV) has been established as the causative agent of the acquired immunodeficiency syndrome (AIDS) for over twentysix years now (Barré-Sinoussi et al., 1983). During this time, an unprecedented success has been achieved in discovering anti-HIV drugs as reflected by the fact that there are now more drugs approved for the treatment of HIV than for all other viral infections put together (Mehellou, De Clercq, 2009). Despite this progress...

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“…Microbial transformation studies have been conducted successfully as model systems to predict metabolic pathways in humans or to increase the efficiency of drugs by metabolic activation 1,2 . However, it was not until 1955 that a systematic study of steroid transformations by microorganisms belonging to the same genus was reported.…”

Section: Introductionmentioning

confidence: 99%