P38 MAPK Pathway were randomly assigned to one of two treatment groups

Study with 20 subjects, when a failure p38 MAPK Pathway rate of 15% has occurred. Subject recruitment was done by a computerized randomization and web-based enrolmentsystem. The subjects were randomly assigned to one of two treatment groups sequences for the periods 1 and 2: treatment A followed by B or B treatment followed by treatment A. In both treatment periods neratinib at about 8.00 clock was administered after a night of drinking I Have at least 10 hours. The day was administered neratinib considered day 1 of treatment period. For treatment B, the first dose of ketoconazole was in the evening about 12 hours before administration of neratinib early and the second dose was administered on day 1 in combination with neratinib about 20.00 clock, the third fourth and fifth dose administered 400 mg of ketoconazole were at about 08.00 clock on days 2, 3 and 4 The two study periods were administered by a W Scheme of 13 days between doses separated neratinib. The subjects were discharged from the study center after the blood PK last day of each period of 5 days / 4 RIGHTS in the hospital. Neratinib was provided in the form of capsules provided 80 mg of ketoconazole than three and two 200 mg tablets. And safety reps Possibility have been reported on the basis of signs and symptoms that k Rperliche study examined vital sign measurements, ECG, and the results of clinical laboratory tests. The treatment of adverse events were events that have taken place, any time after the first dose of study medication until 15 days after the last dose of study medication each, independently Ngig of relationship to study drug. The sampling and analytical methods for the two study periods was tive samples of 5 ml This blood from a catheter or by direct venipuncture into EDTA-R Hrchen Treated with potassium 0, 0 collected, 5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours after injection neratinib for the quantification of plasma concentrations neratinib. Hrchen The contents of the R Gently mixed and the R Hrchen were were immediately placed on ice. The samples were processed within 15 minutes after collection at approximately 1000 g for 10 min centrifuged at 4.
The separated plasma was sealed on Polypropylenr Hrchen transferred and 70 frozen until the pipes were shipped on dry ice Bioanalytical Services, LLC for the test Covance. Plasma samples were analyzed by a validated neratinib liquid chromatography / mass spectrometry assay in tandem with 0.25 ml of plasma. The method is linear over the range 3.00 to 250 ng ml was 1 and the lower limit of quantification of 3 ng ml 1.Proteins from the plasma was removed and replaced by F precipitation neratinib and internal standard, WAY 178357, acetonitrile: methanol were molecules on a C18-S using Genesis mobile phases of 50 mM ammonium acetate isolated. The detection was performed using a Sciex API 4000 mass spectrometer with an interface Ionenzerst Pollination Turbo, which was operated in positive ion mode with multiple reaction monitoring with the mass-Trnsfer Length of 557.2112.2 574.2339.0 neratinib and for the internal standard . No st Rende peaks occurred in the areas of interest that have influenced the data significantly. Contr for low, medium and high samples The quality of t, which were analyzed with the samples of the study, the dosage ranged between 96.1% to 104.0%, and as the inter-war period.