On are summarized in Table 2. within 3 to 4 hours after oral administration. Plasma concentrations of apatinib varying amounts to Chtlich between patients. For example, the C max values differ 926-4625 ng / mg ml after a single dose of 750th There was strong international patients. The plasma concentration of apatinib erh Ht with dose. CEP-18770 Proteasome Inhibitors Cmax and AUC0 24 showed a dose- Independent increase in doses ranging from 500 to 850 mg erh ht And slightly more than the dose at a dose of 850 mg and showed a big inter-individual variability of e t. The half-life of the terminal phase, at about 9 clock shops protected, was constant in all three dose levels.
For the evaluation of multiple doses of 750 mg, Cmax was 2421 ng / ml on day 1, the 2553 ng / ml on day 6 increased Ht and the mean AUC 0 19 399 �� was 24 ng / ml on day 1, increased the ht to 25 449 ng �� / ml at day 6 There was no further increase in Cmax and AUC over 6 days of multiple doses, and it was Similar to the mean elimination half-life t1 / 2 The steady state was achieved by erismodegib NVP-LDE225 day 6, suggesting no accumulation may need during the 56 days of treatment once t Possible. Table 1 Patient demographic data and clinical characteristics of patients characterized by m No Sex Nnlich 26% Female 56.5 43.5 20 Age, 51 years Average range 23 68 0 8 17.4 78.3 ECOG-PS 2nd January 36 February before therapy 4.3 46 1 21 2 chemotherapy 10th M March, 15 radiotherapy surgery 13 39 Other 7 measurability of the underlying disease measurable Not measurable 45 97.8 1 2.1 Place of primary gastrointestinal tract Rtumors 34 73.
9 bronchus / lung 3 6.5 3 6.5 Other 13th June Abbreviation: ECOG, Eastern Cooperative Oncology Group Table 2 are not compartmental pharmacokinetic parameters of average Apatinib after single or multiple oral doses of PK parameters, single oral dose multi-dose oral 750 mg 500 mg 750 mg 850 mg on Day 1, Day 6 Day 28 Day 56 Cmax, ng / ml Geometric Mean 1,521 2,379 2,833 2,421 2,553 2,210 1,854 75.1 55.9 90.0 68.5 51.2 52 8 45.5% CV time tmax median 3.5 3.0 4.0 3 0 4.0 4.0 3.0 3.0 8.0 2.0 4.0 1.5 range 8 0 2.0 8.0 3.0 8.0 2.0 6.0 2.0 6.0 AUC0 24, ng �� / ml geometric mean 11,295 18,172 21,975 19,399 25,449 19,946 15,629 69.7 59% CV, 3 80.8 60.5 59.2 43.2 63.2 t1/2lz, average hours 8.1 9.0 9.1 8.9 11.0 11.3 8.3 30.7 15%, CV 33.1 25.8 56.7 66.5 61.
0 Abbreviations: C max, maximum plasma concentration , CV, coefficient of variation, tmax, Cmax to achieve time, AUC0 24, the liquid che assigned under the curve plasma concentrations ranging from 0 to 24 hours, t1/2lz, the half-life of the slope of a curve concentration-time-terminal half log. Li et al. BMC Cancer 2010, 10:529 2407/10/529 Page 4 of 8 toxicity T and tolerance of Bev Lkerung safety included all patients who again U at least one dose of apatinib. The most hours Ufigsten drug-related adverse events observed hypertension, proteinuria, and hand-foot syndrome. Hypertension was manageable with antihypertensive drugs. About 10% of patients developed grade 3 HFS has progressed. The application of lotions or moisturizers was useful for the relief of the symptoms Mine. Antibiotic creams were introduced when the infection was found. The H Contain FREQUENCY by all UEs associated with the treatment for each dose in Table 3. Treatment-related adverse events were Table 3 H FREQUENCY of treatment-related side effects in the study population cohort for each adverse event