Current Drug Metabolism (v.17, #9)

Meet Our Editorial Board Member by A. David Rodrigues (835-835).

Drug Metabolism and Pharmacokinetics of Dammarane Triterpenoids by Sainan Zhang, Yuqing Zhao (836-848).
Dammarane triterpenoids are widely distributed in plants and are implicated in various bioactivities and pharmacological effects. This review focuses on advancements in dammarane triterpenoid metabolism, particularly drug design and development, including radiolabeling, absorption, distribution, metabolism, excretion, and pharmacokinetics, which can accurately describe the behaviors of dammarane triterpenoids. This review contributes to the systematic and consistent research and development of dammarane triterpenoids. Their structures and activities, radiolabel application, absorption, distribution, and pharmacokinetic characteristics, possible degradation pathways, metabolic enzyme induction or inhibitory effect, and structure-activity relationships have been described. New intranasal and intra-tympanic administration routes and microdialysis technology have also been introduced. These techniques not only improve the limits of dammarane triterpenoids on absorption and distribution but also facilitate the design and study of these compounds as potential drugs.

Owing to the straightforward synthesis, good biological compatibility, and ease of surface functionalization, gold nanoparticles (AuNPs) have shown great potential in various biomedical applications, including diagnostic imaging, photothermal therapy (PTT), and drug delivery. Physicochemical properties (e.g. shape, size and surface chemistry) may potentially affect the interaction of AuNPs with biological systems, thus ultimately influencing their cell uptake, pharmacokinetics, biodistribution, drug delivery efficiency, and biological effects. This review focuses on recent advances in understanding the relation between physicochemical characteristics of AuNPs and their navigation through different biological processes, including biodistribution, penetration of biological barriers (e.g. blood-brain barrier), clearance, and metabolism. Furthermore, the in vitro and in vivo toxicological effects of AuNPs and their possible mechanisms were discussed. A thorough understanding of these influencing factors will be crucial for the rational design, customized functionalization, and clinical translation of AuNPs in drug delivery.

Human genome sequencing highlights the involvement of genetic variation towards differential risk of human diseases, presence of different phenotypes, and response to pharmacological elements. This brings the field of personalized medicine to forefront in the era of modern health care. Numerous recent approaches have shown that how variation in the genome at single nucleotide level can be used in pharmacological research. The two broad aspects that deal with pharmacological research are pharmacogenetics and pharmacogenomics. This review encompasses how these variations have created the basis of pharmacogenetics and pharmacogenomics research and important milestones accomplished in these two fields in different diseases. It further discusses at length their importance in disease diagnosis, response of drugs, and various treatment modalities on the basis of genetic determinants.

Genetic and Non-Genetic Determinants of the Pharmacological Activity of Statins by Marta Karazniewicz-Lada, Anna Glowka, Jakub Mikolajewski, Juliusz Przyslawski (877-896).
Statins are cholesterol-lowering agents which belong to the group of the most commonly prescribed drugs. The use of statins has become the standard treatment in patients with an increased risk of cardiovascular and coronary heart diseases. However, many clinical studies have shown that 13 - 75% of patients fail to achieve LDL-cholesterol and total cholesterol target levels. The clinical implications of insufficient response include cardiovascular complications caused by atherosclerosis leading to acute myocardial infarction, stroke and death. The mechanism underlying statin resistance has been associated with genetic polymorphisms and nongenetic factors (e.g. concomitant diseases, drug-drug interactions, interactions with food and dietary supplements). The article provides a comprehensive update of the current knowledge regarding the role of genetic polymorphism and non-genetic determinants of cholesterol-lowering effect of statins. Dietary aspects of statin efficacy were also presented. The Pubmed search was performed to identify relevant papers from the last ten years which were included in the review. Consideration of the genetic and non-genetic determinants of pharmacological action of statins as well as mechanisms of drug-drug interactions may be useful in clinical practice for improving safety and efficacy of statin treatment.

Leishmaniasis is one of the six diseases regarded most neglected by World Health Organization which is predominant in developing countries. Clinically, among the different forms of leishmaniasis, visceral leishmaniasis is the most fatal, serious disease, in which several organs of the body such as liver and spleen are affected. A limited number of drugs against leishmaniasis are available for the treatment and also, no suitable vaccine is available for the control of leishmaniasis. However, the drugs currently used for the treatment of leishmaniasis have serious side effects as well as drug resistance issues. Therefore, search for alternative drugs to treat leishmaniasis is widely pursued; often targeting the metabolic pathways of Leishmania which are either absent or different from the mammalian host and involved in survival, pathogenesis and drug resistance of parasite. Herein, we review the aspects of chemotherapy of leishmaniasis by synthetic and natural drugs, their mechanism of action, pharmacokinetics and involvement in the development of drug resistance. Furthermore, regulatory role of trypanothione as key molecule for redox homeostasis via antioxidant enzymes and proteins like tryparedoxin, tryparedoxin peroxidase, superoxide dismutase, and ascorbate peroxidase are presented. We have comprehensively discussed thiol metabolism as drug target and its role in parasite survival.