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It is my great pleasure to introduce Drug Metabolism Letters (DML; www.bentham.org/dml) to the Readers as a unique journal in the field, which has gained recognition among its audience within a very brief span of time since its launch back in January 2007. The journal has already been accepted for coverage in Chemical Abstracts, EMBASE, EMBiology and Scopus! DML publishes short papers/letters on major advances in all areas of drug metabolism and disposition. Its publisher, Bentham Science, publishes more than 250 print and open access journals (www.bentham.org), (www.bentham.org/open) and books (www.bentham.org/ebooks).

The journal board comprises nine Associate Editors, forty-five Editorial Board Members and forty-three Reviewers. Each Associate Editor of DML handles peer reviewing of papers received from his/her region on behalf of the Editor-in-Chief.

The journal is also publishing one issue each year dedicated to submissions from the Editorial Board Members of DML. This is the first such issue and I congratulate to all the contributing Editorial Board Members for their positive response and hope they will continue to participate in each year's issue. I hope this will prove to be valuable for all readers by helping them to identify with some Editorial Board Members when submitting their work to DML. The contributions in this issue were subjected to the same peer review process as all manuscripts followed by desired revisions.

I do hope the DML Reader will find all twelve papers included in this issue, to be quite interesting:

Urs A. Boelsterli et al.. studied the bioactivation of leflunomide and the metabolic degradation to its major metabolite, A771726. Leflunomide was rapidly metabolized in human hepatocytes to A771726, but its toxicity was dependent on other, CYP-dependent intermediates. James F. Rusling and colleagues used rat liver microsomes attached to nanoparticles for LC-MS studies of CYP3A and 2E1 enzymes in metabolism of N-nitroso compounds. Using these biocolloids, turnover rates were measured within 2 min. Inhibitor IC50 values for ketoconazole (KET) and 4-methylpyrazole (4-MEP) were also estimated. Lee Jia et al. investigated the effects of CsA and ITZ on 1) intestinal permeability of amlodipine (a calcium channel blocker used as a cardiovascular agent) in isolated rat everted gut sac model, and 2) biliary excretion and pharmacokinetics of amlodipine in rats. Pretreatment of rats with ITZ increased plasma levels and biliary excretion of amlodipine in a dose-dependent manner. In contrast, pretreatment with CsA slightly decreased biliary excretion of amlodipine and made no changes in its plasma levels.

Michael W. Sinz et al. demonstrated that the humanized SXR mouse can be used as a model to predict human CYP3A4 induction and the resulting pharmacokinetic changes of CYP3A4 substrates in humans. Jasminder Sahi et al. compared AO activity in cytosol and cryopreserved hepatocytes from human, monkey, rat and mouse livers to assess species differences. They also evaluated possible species differences in drug interactions using seven drugs known to inhibit human cytosolic AO i.e. raloxifene, perphenazine, menadione, maprotiline, ketoconazole, erythromycin, and estradiol. Their data showed major differences in the rate of AO metabolism, and inhibition of AO across species, indicating that results from animal studies cannot be safely extrapolated to humans.

David Rodrigues et al. worked on troglitazone (TGZ) induced hepatotoxicity, which has been linked to cytochrome P450 (CYP)- catalyzed reactive metabolite formation. They concluded that both CYP3A4/5 and CYP2C8 play a major role in the formation of TGZ adduct in HLM. However, the contribution of these CYPs varies depending on their relative expression and the concentration of TGZ.
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Document Type: Research Article

Publication date: August 1, 2008

More about this publication?
  • Drug Metabolism Letters publishes short papers on major advances in all areas of drug metabolism and disposition. The emphasis will be on publishing quality papers very rapidly. Letters will be processed rapidly by taking full advantage of the Internet technology for both the submission and review of manuscripts. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites, reactive intermediate and glutathione conjugates.
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