to CTCAE v3, and coded by the medical dictionary Regulierungst ACTIVITIES 1.0. Pharmacokinetic and pharmacodynamic evaluation of pharmacokinetic sampling took place prior to dosing and at 0.5, 1, 2, 3, Asiatic acid 4, 6, 8 and 24 h after a single dose of 1D1 linifanib cycle, and pre-and dose of 0, 5, 1, 2 , 3, 4, 6 and 8 hours after the administration of multiple doses of once daily C1D15. Urine was collected over 24 hours after dosing C1D15. Linifanib and metabolite concentrations in plasma and urine were measured with a validated method based on mass spectrometry Triple Quadruple tandem with a lower limit of quantification of 1.0 ng mL. Concentrations, pharmacokinetic parameters were determined by compartmental analysis using WinNonlin v.5.2 unprofessional.
Dosisproportionalit T was determined by linear regression analysis of the dose normalized observed peak plasma concentration and the liquid surface Under the curve of the DN plasma concentration 0 24 hours and C1D1 DN DN Cmax and rated AUC24 of C1D15 with doses of 0, 05, 0.1, 0, 2 and 0.25 mg kg. Other samples were taken every second Cediranib and C3D1 study until the end or until C15D1. The sample concentrations for samples ff C3D1 C1D1 to C1D15 data were included in the study non-linear mixed effects covariates such as age, K Body weight and gender. Linifanib after a single dose of 0.25 mg kg, a post-hoc analysis compared the pharmacokinetics between patients in the present study, Japanese and non-Japanese patients in two Phase 1 studies: non-Caucasian patients and 0.25 mg linifanib segment -Japanese Asian patients 0.
10 0.30 mg kg linifanib. Plasma biomarker analysis were collected before the administration of linifanib C1D1, C1D15, C2D1, and at the last visit. PlGF concentration was determined using Abbott Architect kits. The relationship between the levels of PlGF results were analyzed retrospectively. The relationship between PlGF induction and toxicity Judge t, the patients were divided into those who do not need treatment interruption w Grouped during the first 30 days of treatment. PlGF median increase between the beginning and according C1D15 were the group of toxicity compared t. The relationship between PlGF induction and assessment of the efficacy, patients were divided into those with progressive disease or stable disease at C6, and increased Ht baseline PlGF C1D15 was compared.
Statistical analysis Continuous variables from the clinical data were summarized by the number of observations, mean, standard deviation, median, maximum and minimum. Discrete variables were summarized by H Abundance and percentage. Statistical significance for clinical and pharmacokinetic analysis was determined by a 2-sided p-value of 0.05. Results Patient characteristics from September 2008 to September 2009 18 patients with various solid tumors in the NCCH in Japan were part. Linifanib anf Ngliche dose for each patient were kg 0.05 mg, 0.10 mg kg, kg 0.20 mg kg and 0.25 mg. Basic patient and every disease