Abstract:
:Cabozantinib capsules (COMETRIQ) are approved for the treatment of patients with progressive metastatic medullary thyroid cancer. Cabozantinib tablets are investigational drug products considered to be potentially preferred pharmaceutical dosing forms. Two phase I open-label single-dose studies in healthy individuals were carried out to characterize the plasma pharmacokinetics of cabozantinib capsule and tablet formulations: a two-way crossover bioequivalence study (n=77) comparing the tablet formulation and the marketed capsule formulation at the approved 140 mg dose and a dose-proportionality study (n=21 per treatment arm) evaluating the 20, 40, and 60 mg tablet strengths. In the bioequivalence study, plasma exposure [area under the plasma concentration-time curve (AUC0-t and AUC0-inf)] values were similar (<10% difference) for both formulations and the 90% confidence intervals (CIs) around the ratio of geometric least-squares means (GLSM) were within the accepted bioequivalence limits of 80-125%. However, the GLSM for Cmax was 19% higher for the tablet formulation and the upper 90% CI for the ratio of GLSM (131.65%) was beyond the 80-125% range. Thus, the tablet and capsule formulations failed to fulfill the bioequivalence study acceptance criteria. In the dose-proportionality study, single doses of the 20, 40, and 60 mg cabozantinib tablet strengths showed dose-proportional increases where the 95% CIs for the slopes of the ln-transformed Cmax, AUC0-t, and AUC0-inf values versus ln-transformed cabozantinib dose included the value of 1. These findings indicate that cabozantinib plasma exposures increased proportionally with increasing cabozantinib dose over the 20-60 mg tablet strength dose range.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Nguyen L,Benrimoh N,Xie Y,Offman E,Lacy Sdoi
10.1097/CAD.0000000000000366subject
Has Abstractpub_date
2016-08-01 00:00:00pages
669-78issue
7eissn
0959-4973issn
1473-5741journal_volume
27pub_type
杂志文章,随机对照试验abstract::The antitumor action of bestatin is considered to be an indirect action mediated by T-cells. Therefore, we investigated the effects of bestatin on the differentiation and proliferation of human precursor T-cells using a colony formation technique. Bestatin did not increase the overall number of T-cell colonies, but it...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199102000-00005
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abstract::Tafluposide (F 11782), a novel epipodophylloid with a unique mechanism of interaction with both topoisomerase I and II, has shown outstanding antitumor activity in vivo against a panel of experimental human tumor xenografts. The aim of this study was to evaluate its cytotoxicity against fresh tumor cells taken from pa...
journal_title:Anti-cancer drugs
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doi:10.1097/00001813-200307000-00013
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199306000-00015
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199404000-00007
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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