Editorial [Special Board Members Issue]

This is the second issue of ‘Current Drug Metabolism’ reporting on a variety of areas of drug metabolism contributed by the Editorial Board Members of the journal. The journal, publishing its tenth volume, has received impact factor 4.35 in 2009!! Another milestone development is the launch of a new online manuscript submission and processing system, Contents Management System (CMS; http://bentham-editorial.org). I am sure you will find papers in this issue quite interesting to read: Lin et al presents a review on current knowledge of the ADME processes that govern the pharmacokinetics of biotech drugs. In addition, molecular mechanisms of biodistribution, metabolism and renal excretion of biotech drugs have also been discussed. Gomez-Lechon et al find an association between increased lipid deposition and impaired CYP enzymes. This paper presents an overview of the impact of steatosis in the liver's drug-metabolizing capability. Moreover, the possible molecular mechanisms involved in the transcriptional regulation of the CYP expression in fatty liver are explained. Yamazaki et al summarized the expected physiological significance of the biotransfornation as well as Michaelis-Menten constants (Km), maximal velocities (Vmax), Vmax/Km (intrinsic clearance) values, and/or metabolic activities for 33 endogenous substrates, including (1) arachidonic acid and fatty acids, (2) steroid hormones, such as testosterone, progesterone, and allopregnanolone, (3) amines, such as tyramine, and (4) lipid-soluble vitamins, such as retinol and vitamin D3 analogues, mediated human P450 isoforms consisting of so-called drug-metabolizing enzymes for the purpose of predicting the key enzyme(s) in vivo. Zhou et al have contributed four papers in this issue delineating human cytochrome P450 from structure, function, and regulation to Substrate Specificity and Polymorphism. In the first paper entitled “Insights into the Structure, Function, and Regulation of Human Cytochrome P450 1A2” by Zhou et al .discuss about the knockout of CYP1A2 in mice, leading to inventing a useful tool for the functional investigation of this gene. The second paper entitled “Substrate Specificity, Regulation, and Polymorphism of Human Cytochrome P450 2B6” Zhou et al updates our knowledge about the structure, function, regulation and polymorphism of CYP2B6. There is a wide interindividual variability in the expression and activity of CYP2B6. Such a large variability is probably due to effects of genetic polymorphisms and exposure to drugs that are inducers or inhibitors of CYP2B6. The CYP2A6 gene spans a region of approximately 6 kb pairs consisting of 9 exons and has been mapped to the long arm of chromosome 19 (between 19q12 and 19q13.2). In the third review entitled “Structure, Function, Regulation and Polymorphism of Human Cytochrome P450 2A6” By Zhou etal both in vitro and in vivo studies demonstrated a wide (20- to >100-fold) interindividual variation in CYP2A6 expression and activity, which is due primarily to genetic polymorphisms in the CYP2A6 gene. Also, polymorphism of CYP2A6 has been associated with smoking behavior, drug clearance and lung cancer risk. The fourth review entitled “Genetic Polymorphism of the Human Cytochrome P450 2C9 Gene and its Clinical Significance” by Zhou et al devoted to CYP2C9. CYP2C9 is one of the clinically significant drug metabolising enzymes that demonstrates genetic variants with significant phenotype and clinical outcomes. Genetic testing of CYP2C9 is expected to play a role in predicting drug clearance and conducting individualized pharmacotherapy. Papers for the 2010 Board Members Issue are awaited by the end of 2009. I appreciate efforts from the Editorial Office and wish them and the journal all the best.