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

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.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

Physically Similar Systems - A History of the Concept

PreprintThe concept of similar systems arose in physics, and appears to have originated with Newton in the seventeenth century. This chapter provides a critical history of the concept of physically similar systems, the twentieth century concept into which it developed. The concept was used in the nineteenth century in various fields of engineering (Froude, Bertrand, Reech), theoretical physics (van der Waals, Onnes, Lorentz, Maxwell, Boltzmann) and theoretical and experimental hydrodynamics (Stokes, Helmholtz, Reynolds, Prandtl, Rayleigh). In 1914, it was articulated in terms of ideas developed in the eighteenth century and used in nineteenth century mathematics and mechanics: equations, functions and dimensional analysis. The terminology physically similar systems was proposed for this new characterization of similar systems by the physicist Edgar Buckingham. Related work by Vaschy, Bertrand, and Riabouchinsky had appeared by then. The concept is very powerful in studying physical phenomena both theoretically and experimentally. As it is not currently part of the core curricula of STEM disciplines or philosophy of science, it is not as well known as it ought to be