Increased R & D spending and high failure rates exist in drug development, due in part to inadequate prediction of drug metabolism and its consequences in the human body. Hence, there is a need for computational methods to supplement and complement current biological assessment strategies. In this review, we provide an overview of drug metabolism in pharmacology, and discuss the current in vitro and in vivo strategies for assessing drug metabolism in preclinical drug development. We highlight computational tools available to the scientific community for the in silico prediction of drug metabolism, and examine how these tools have been implemented to produce drug-target signatures relevant to metabolic routes. Computational workflows that assess drug metabolism and its toxicological and pharmacokinetic effects, such as by applying the adverse outcome pathway framework for risk assessment, may improve the efficiency and speed of preclinical drug development.

The field of systems biology, termed systems toxicology when applied to the characterization of adverse outcomes following chemical exposure, seeks to develop biological networks to explain phenotypic responses. Ideally, these are qualitatively and quantitatively similar to the actual network of biological entities that have functional consequences in living organisms. In this review, computational tools for predicting chemicalprotein interactions of multi-target compounds are outlined. Then, we discuss how the methods of systems toxicology currently draw on those interactions to predict resulting adverse outcomes which include diseases, adverse drug reactions, and toxic endpoints. These methods are useful for predicting the safety of drugs in drug development and the toxicity of environmental chemicals (ECs) in environmental toxicology.

Aflibercept is the most recently approved vascular endothelial growth factor (anti-VEGF) inhibitor for the management of diabetic macular edema and diabetic retinopathy. The purpose of this article is to review the efficacy and safety of aflibercept in the management of diabetic eye complications and to describe its place in therapy. Anti-VEGF agents have been noted in clinical trials to be superior to laser photocoagulation, the standard therapy ( P < .0001, P ≤ .0085, respectively). Aflibercept has been comparatively studied with other anti-VEGF agents, namely, bevacizumab and ranibizumab, and noted to be equally efficacious and safe in patients with mild visual acuity loss ( P > .50). However, in the treatment of patients with diabetic macular edema having moderate to severe visual acuity loss, aflibercept outperformed the other 2 anti-VEGF agents (aflibercept vs bevacizumab, P < .001; aflibercept vs ranibizumab, P = .003). However, additional studies are needed to fully appreciate the long-term safety and efficacy of aflibercept and the anti-VEGF therapy class.