Drugs that flow from humans into the environment may include the lingering analgesic diclofenac, the long-lasting antiepileptic carbamazepine, the omnipresent antibiotic ciprofloxacin, and even seemingly mundane painkillers like ibuprofen, gemfibrozil, and naproxen, not to mention synthetic estrogens. The problem has led to government hearings at the state and federal levels and to scientific m...

A series of studies were conducted to explore the mechanism of the pharmacokinetic interaction between simvastatin (SV) and gemfibrozil (GFZ) reported recently in human subjects. After administration of a single dose of SV (4 mg/kg p.o.) to dogs pretreated with GFZ (75 mg/kg p.o., twice daily for 5 days), there was an increase (approximately 4-fold) in systemic exposure to simvastatin hydroxy a...

BACKGROUND AND OBJECTIVES Two phase I drug interaction studies were performed with oral enzalutamide, which is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). METHODS A parallel-treatment design (n = 41) was used to evaluate the effects of a strong cytochrome P450 (CYP) 2C8 inhibitor (oral gemfibrozil 600 mg twice daily) or strong CYP3A4 inhibitor (oral ...

BACKGROUND We studied the joint effect of baseline triglyceride and lipoprotein cholesterol levels on the incidence of cardiac end points in the trial group (n = 4,081) of the Helsinki Heart Study, a 5-year randomized coronary primary prevention trial among dyslipidemic middle-aged men. The relative risks (RR) were calculated using Cox proportional hazards models with a dummy variable technique...

Desloratadine (Clarinex), the major active metabolite of loratadine (Claritin), is a nonsedating long-lasting antihistamine that is widely used for the treatment of allergic rhinitis and chronic idiopathic urticaria. For over 20 years, it has remained a mystery as to which enzymes are responsible for the formation of 3-hydroxydesloratadine, the major active humanmetabolite, largely due to the i...

Os agonista dos PPARs lesam o Complexo I da cadeia de elétrons mitocondrial a NADH citocromo-c redutase provocando aumento da geração de radicais livres de oxigênio, lesão do DNAmt e diminuição da produção de ATP mitocondrial o que desvia o metabolismo para glicólise anaeróbia, motor da proliferação celular maligna. Este efeito de lesão do Complexo I é leve com os fibratos – agonistas alfa (clo...