Special Issue "Feature Papers"

Assistant Editor
Ms. Demi Liu
MDPI Haidian Office, Yingu Mansion, Suite 815, North 4th Ring Road West, 9, Haidian District, Beijing 100190, China
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Phone: +86 10 6280 0830

Submission

All manuscripts should be submitted to pharmaceutics@mdpi.com with a copy to the Guest Editor. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. For the first couple of issues, to be published in 2009 and 2010, the Article Processing Charges (APC) will be waived for well-prepared manuscripts. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Type of Paper: Article
Title: Expression of drug-resistant factor gene in hepatocellular carcinoma patients prior to chemotherapy with platinum complex by arterial infusion
Authors: Tomoya Sakurada ¹, Masaharu Yoshikawa ², Masahiko Sunaga ³,Eriko Kobayashi ¹, Nobunori Satoh ⁴ , Osamu Yokosuka ² and Shiro Ueda ¹
Affiliations: ¹ Department of Drug Information and Communication, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan; ² Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675 Japan; ³ Department of Gastroenterology, Chiba Central Medical Center, 1835-1 Kasoricho, Wakaba-ku, Chiba, 264-0017 Japan; ⁴ Department of Clinical Education and Research, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan; E-Mail: sakurat@p.chiba-u.ac.jp
Abstract: This study investigated the drug resistance factor gene expression in biopsy tissue samples from hepatocellular carcinoma (HCC) patients prior to chemotherapy by platinum complex. Furthermore, the relationship between gene expression and therapeutic effect was retrospectively investigated to assess any possibility of predicting the therapeutic effect based on the drug-resistant factor gene. The subjects of this study were 35 HCC patients who were to receive chemotherapy with platinum complex by arterial infusion. Liver biopsy was performed to collect tissue from the tumor site and the non-tumor site prior to the start of treatment. For drug-resistant factors, drug excretion transporters cMOAT and MDR-1, intracellular metal binding protein MT2, DNA repair enzyme ERCC-l and inter-nucleic cell transport protein MVP were investigated. Using cDNA obtained by reverse transcription as the template, the expression of each resistant factor was determined by quantitative PCR method using Light CyclerⓇ. The comparison of drug-resistant factor gene expression between the tumor site and the non-tumor site indicated a significant decrease of MT2 and MDR-1 in the former while a significant increase in ERCC-1 was noted in the former. The drug-resistant factor gene expression was compared between the response cases and non-response cases using the ratios of cMOAT and MT2 expression in tumor site to the expression in non-tumor site. With cut-off values set at 1.5 and 1.0, the patients were classified into the high expression group and low expression group respectively, the response rate in the former was significantly lower in the latter. As the next step, the cut-off values of cMOAT and MT2 were combined and the patients were classified into A group (cMOAT≧1.5 or MT2≧1.0) and B group (cMOAT＜1.5 and MT2＜1.0). The response rate in the former was significantly lower than in the latter. The difference between the response cases and non-response cases in the expression of ERCC-1, MDR-1 and LRP was not significant. The substantial involvement of cMOAT and MT2 was strongly correlated with the effect of treatment with platinum complex. It is considered possible to estimate the therapeutic effect of platinum complex at a high probability by combining the expression condition of these 2 genes.

Type of Paper: Article
Title: Induction of P-glycoprotein adversely affects pharmacokinetics of risperidone- a study in mice
Authors: David Holthoewer, Christoph Hiemke and Ulrich Schmitt
Affiliation: Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg- University Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, Germany; E-Mail: schmitt@psychiatrie.klinik.uni-mainz.de
Abstract: Pharmacokinetic interactions, e.g. P-glycoprotein efflux transport, at the blood-brain barrier can be a reason for treatment non-response. This study focuses on the influence of a P-glycoprotein induction on the pharmacokinetics of the P-glycoprotein substrate risperidone. Brain and serum levels of risperidone and its active metabolite 9-hydroxyrisperidone, which is also a P-glycoprotein substrate, were measured after P-glycoprotein induction with rifampicin, dexamethasone or 5-pregnene-3beta-ol-20-on-16alpha-carbonitrile (PCN) using high performance liquid chromatography. The active moiety, sum of risperidone and 9-hydroxyrisperidone, was dramatically decreased in mouse brain and serum after P-glycoprotein induction. Metabolism and distribution of risperidone active moiety have also been affected.