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Mutation Research. Genetic Toxicology... Mar 2015The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect genotoxic hepatocarcinogens that can be integrated into a general...
The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect genotoxic hepatocarcinogens that can be integrated into a general toxicity study. The assay methods were thoroughly validated by 19 Japanese facilities. Methapyrilene hydrochloride (MP), known to be a non-genotoxic hepatocarcinogen, was examined in the present study. MP was dosed orally at 10, 30 and 100mg/kg/day to 6-week-old male Crl:CD (SD) rats daily for 14 days. Treatment with MP resulted in an increase in micronucleated hepatocytes (MNHEPs) with a dosage of only 100mg/kg/day. At this dose level, cytotoxicity followed by regenerative cell growth was noted in the liver. These findings suggest that MP may induce clastogenic effects indirectly on the liver or hepatotoxicity of MP followed by regeneration may cause increase in spontaneous incidence of MNHEPs.
Topics: Administration, Oral; Age Factors; Animals; Body Weight; Bone Marrow; Carcinogens; Chromosome Aberrations; Cooperative Behavior; Dose-Response Relationship, Drug; Drug Administration Schedule; Hepatocytes; Humans; Japan; Liver; Male; Methaqualone; Micronucleus Tests; Organ Specificity; Rats; Rats, Sprague-Dawley; Reticulocytes; Societies, Pharmaceutical
PubMed: 24768639
DOI: 10.1016/j.mrgentox.2014.04.004 -
Archives of Pharmacal Research Jan 2015Amisulpride, a selective antagonist of D2 and D3 dopamine receptors, is used as an antipsychotic drug. In this study, we reported a sensitive LC-MS/MS method for...
Amisulpride, a selective antagonist of D2 and D3 dopamine receptors, is used as an antipsychotic drug. In this study, we reported a sensitive LC-MS/MS method for determining amisulpride concentrations in rat plasma, and a preclinical pharmacokinetic study in the rat. After a simple protein precipitation with acetonitrile containing methaqualone as an internal standard, the analytes were separated on a reversed-phase column with a mobile phase of 0.2 % aqueous formic acid and acetonitrile (3:7, v/v). The accuracy and precision of the assay were in accordance with FDA guidance for the validation of bioanalytical methods. This analytical method was used successfully to characterize the time course of the plasma concentration of amisulpride following oral administration of a single 10 mg/kg dose in rats.
Topics: Administration, Oral; Amisulpride; Animals; Chromatography, High Pressure Liquid; Drug Stability; Rats; Sulpiride; Tandem Mass Spectrometry
PubMed: 24619919
DOI: 10.1007/s12272-014-0361-1