A review of pharmacokinetic parameters of metabolites and prodrugs

In drug discovery and development, the kinetic study of active metabolites plays an important role, helping to define the time course of the drug in the body and its activity or toxicity. After a pharmacokinetics assessment of a drug and its metabolite or a prodrug and its parent-drug, several parameters can be calculated. In some cases, achieving the objective of the study does not require all possible parameters to be calculated. When parameters are calculated, it is essential that their denotations are widely accepted and used. However, some parameters undergo a certain variability of denotation, which may confuse some readers. Thus, this review summarizes the current published data for experimental pharmacokinetic parameters of metabolites and the calculations involved in simple metabolite pharmacokinetic studies. It also evaluates the most common pharmacokinetic parameters in the literature and suggests metabolite parameters that could be determined to help advance metabolite kinetic models.

Thiophenecarboxamide derivatives activated by EthA kill mycobacterium tuberculosis by inhibiting the CTP synthetase PyrG

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Overexpression of mitochondrial uncoupling protein 1 (UCP1) induces a hypoxic response in Nicotiana tabacum leaves

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influência do exercício físico na remodelação cardíaca induzida pelo ácido retinóico

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Poluentes orgânicos persistentes em ar interior: desenvolvimento de método de extração em adsorvente para amostragem ativa

Persistent Organic Pollutants (POPs) are chemical substances extraordinarily toxic and persistent in the environment. Due to these properties, POPs are targets of the Stockholm Convention which aims to provide means to eliminate production and use by encouraging the reduction and, where possible, eliminating the release of these contaminants to the environment. One of the articles of this _Convention aims to assess the basal levels of such substances in the environment to monitor both the reduction of release to the environment, and to assess human exposure, using analyzes of milk and air for example. Although efforts to control POPs production and release to the environment have been made, data about their levels in Brazil are still scarce, mainly in the atmosphere or indoor environment. Considering the permanence of people inside its house, this study presents a method for POP extraction from XAD-2 sorbent employed in indoor air sampling, with identification and quantification by GC-ECD. GC-ECD linear range of the studied analytes, congeners of polychlorinated biphenyls (PCB) (28, 52, 101, 118, 138, 153 and 180), DDTs and their metabolites (DDDs, DDEs) and endosullan (isomers c - and 13 - and metabolite endosulfan sulfate) ranged between 0.5 and 16.0 ng mL-I with r2 > 0.967. The method developing consist of selecting the extraction solvent system by agitation (90 rpm, 1 hour) with n-hexan,e (2 mL) or n-hexane:acetone (1:1, v/v) (2 mL), concentration the extract with a gentle N2 stream, and evaluation of breakthrough with passage or air through the fortified XAD-2 cartridge before extraction, employing a low volume air suction pump (Pump Model 224 universal-PCXR8; 5-5000 mL min-1, SKC Inc., Eighty Four, PA, USA), Calibrator Dry-Cal DC-Lite (BIOS, Butler, NJ, USA)). Two fortification levels were employed, 15 and 30 ng. After selecting n-hexane as extraction solvent, with accuracy and precision ranging...

Farmacocinética e farmacodinâmica de derivado ftalimídico planejado para o tratamento da anemia falciforme

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Atividade dos neurônios do núcleo anterovental periventricular e sua participação no envelhecimento reprodutivo de ratas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Diterpenos tetranorlabdanos e isocumarinas produzidos por Botryosphaeria parva, um fungo endofítico em Eugenia jambolana Lam. (Myrtaceae)

Pós-graduação em Química - IQ