Mouse Anti-EDDP monoclonal antibody, clone H12417N

Rice blast disease is the most serious and damaging of all the plant diseases in rice production in such temperate and humid climate like that of Japan, which resulted in the development of many excellent chemicals for this particular disease, e.g., blasticidin S, kasugamycin, iprobenphos (IBP), edifenphos (EDDP), isoprothiolane, ferimzone, and metominostrobin. These chemicals mostly act on the growth of M oryzae by exhibiting specific fungicidal effects on the pathogen. The wide use of these site specific chemicals sometimes causes development of resistance in the pathogens. In fact, resistance against kasugamycin and organophosphorus thiolate fungicides were recognized in the field where they were too intensively used. Solutions to the problem were contrived for the effective use of the chemicals at hand, such as application of mixtures with different action mechanisms or their use in rotation. While all modem fungicides are developed through extensive safety evaluation, there is a deep public concern about their side effects on non-target organisms and on the environment. Thus there is a great deal of interest in non-fungicidal disease controlling agents since they are supposedly specific to target organisms and are less likely to lead to resistance problems. Actually, two groups of non-fungicidal rice blast chemicals are currently on the market; melanin biosynthesis inhibitors (MBIs), e.g., fthalide, tricyclazole, pyroquilon, carpropamid, diclocymet and fenoxanil, and the so called priming effectors or plant defense activators such as probenazole, acibenzolar-S-methyl and tiadmil, which induce host resistance against the pathogen's attack.

The aim of this study was to investigate the possible effect of orally administered isavuconazole, ketoconazole, or voriconazole on the pharmacokinetics of methadone in rats. Twenty Sprague-Dawley (SD) rats were divided randomly into four groups: Group A (control), group B (5 mg/kg isavuconazole), group C (5 mg/kg ketoconazole), and group D (5 mg/kg voriconazole). A single dose of methadone was administrated half an hour later. Methadone in plasma concentrations and its metabolite EDDP in microsomes were determined by ultra-high-performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS), and pharmacokinetic parameters were calculated by DAS version 3.0. The C-max of methadone in groups C and D increased to 2.7-fold and 5-fold, respectively. While AUC increased in three groups and group D increased the most. Also, isavuconazole, ketoconazole, and voriconazole showed inhibitory effect on human and rat microsomes. The inhibition ratios of isavuconazole, ketoconazole, and voriconazole in rat liver microsome were 97.87%, 96.74% and 78.9%, respectively (p < 0.01), while in human liver microsome, inhibition ratios were 86.97%, 96.46%, and 53.11%, respectively. And the IC50 for inhibition activity of isavuconazole, ketoconazole, and voriconazole in rat microsomes were 7.76 mu M, 8.33 mu M, and 4.45 mu M, respectively. Our study indicated that taking methadone combine with ketoconazole, isavuconazole, or voriconazole could reduce the metabolism rate of methadone and prolong the pharmacological effects in vivo and in vitro.