Current Drug Metabolism - Volume 15, Issue 7, 2014

This article reviews in vitro metabolic and in vivo pharmacokinetic drug–drug interactions of nine antifungal agents: six azoles (fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, and voriconazole) and three echinocandins (anidulafungin, caspofungin, and micafungin). In in vitro interaction studies, itraconazole, ketoconazole, and miconazole were found to have higher inhibitory effects on cytochrome P450 Read More

Ocular disorders can significantly lower a patient’s quality of life. Centers for Disease Control and Prevention’s Vision Health Initiative have estimated that the number of people affected by age-related ocular diseases may be doubled in the United States by 2030. Although availability of newer therapeutics has improved the prognosis of ocular diseases, poor ocular bioavailability still remains a major concern. Combinatio Read More

Hepatotoxicity related to antidepressive pharmacotherapy is a major safety concern, particularly considering that severe forms of hepatic failure with fatal outcome have been reported. Severe hepatotoxic adverse drug reactions were also reported for agomelatine (AGM), an antidepressive agent, which was approved for the treatment of major depressive disorder (MDD) in adults by the European Medicines Agency (EMA) in Read More

Multi-drug resistance (MDR) to cancer chemotherapy is a major obstacle to the effective treatment of tumors. Resveratrol, a natural product, may inhibit efflux transporters, such as P-glycoprotein (P-gp), multi-drug resistance-associated protein (MRP) and breast cancer resistance protein (BCRP), and could become a potential multi-drug-resistant regulator. But it remains unclear how resveratrol exerts its reversal effect. In Read More

Interindividual variability in drug response depends on a number of genetic and environmental factors. The metabolic enzymes are well known for their contribution to this variability due to drug-drug interactions and genetic polymorphisms. The phase I drug metabolism is highly dependent upon the cytochrome P450 mono-oxygenases (CYP) and their genetic polymorphism leads to the variable internal drug exposures. The Read More

Background: Cytochrome monooxygenases P450 enzymes (CYPs) are terminal oxidases, belonging to the multi-gene family of heme-thiolate enzymes and located in multiple sites of ER, cytosol and mitochondria. CYPs act as catalysts in drugs metabolism. Areas covered: This review highlights the mitochondrial and microsomal CYPs metabolic functions, CYPs mediated ROS generation and its feedback, bioactivation of Read More

Protein engineering holds the potential to transform the metabolic drug landscape through the development of smart, stimulusresponsive drug systems. Protein therapeutics are a rapidly expanding segment of Food and Drug Administration approved drugs that will improve clinical outcomes over the long run. Engineering of protein therapeutics is still in its infancy, but recent general advances in protein engineering capabilitie Read More