Evidence map›Paper›PMID 27379402›Full record

Trial reportClinical pharmacokinetics2017

Population Pharmacokinetic and Covariate Analysis of Apatinib, an Oral Tyrosine Kinase Inhibitor, in Healthy Volunteers and Patients with Solid Tumors.

Mingming Yu, Zhiwei Gao, Xiaojian Dai, Hui Gong, Lianshan Zhang, Xiaoyan Chen, Da-Fang Zhong, Sherwin K B Sy

Abstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
PubMed Publisher
In one paragraph

Trial report in Clinical pharmacokinetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 29 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Mingming YuState Key Laboratory of Drug Research and Center for Drug Metabolism and Pharmacokinetics Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China.
Zhiwei GaoState Key Laboratory of Drug Research and Center for Drug Metabolism and Pharmacokinetics Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China.
Xiaojian DaiState Key Laboratory of Drug Research and Center for Drug Metabolism and Pharmacokinetics Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China.
Hui GongDepartment of Mathematics and Statistics, Valpraisso University, Valpraiso, IN, USA.
Lianshan ZhangJiangsu Hengrui Pharmaceuticals Co. Ltd., Shanghai, China.
Xiaoyan ChenState Key Laboratory of Drug Research and Center for Drug Metabolism and Pharmacokinetics Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China.
Da-Fang ZhongState Key Laboratory of Drug Research and Center for Drug Metabolism and Pharmacokinetics Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China. dfzhong@simm.ac.cn.
Sherwin K B SyPost-Graduate Program in Biostatistics, Department of Statistics, State University of Maringá, Avenida Colombo, 5790 Bloco E90-sala 221, Maringá, PR, CEP 87.020-900, Brazil. sherwin.kenneth.sy@gmail.com.
Chinese Academy of Sciences · CNShanghai Institute of Materia Medica · CNJiangsu Hengrui Medicine (China) · CNUniversidade Estadual de Maringá · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesApatinib is an oral tyrosine kinase inhibitor approved in China for the treatment of patients with advanced metastatic gastric cancer. The approved dosing schedule is 850 mg once daily. The objective of this study was to develop a population pharmacokinetic (popPK) model of apatinib and determine factors that affect its pharmacokinetics.

methodsA popPK model for apatinib was developed using data from 106 individuals, including healthy volunteers and patients with malignant solid tumors. The potential influence of demographic, patient, and laboratory characteristics on oral apatinib pharmacokinetics were investigated in a covariate analysis. The extent of the impact of significant covariates on the exposure of apatinib was evaluated using simulations.

resultsThe final popPK model was a two-compartment model with mixed first- and zero-order absorption and first-order elimination. The population estimates of apparent clearance (CL/F) and apparent volume at steady-state were 57.8 L/h and 112.5 L, respectively. The non-linear dose proportionality in apatinib relative bioavailability was characterized by a sigmoidal maximum effect (E

conclusionsThe increase in apatinib exposure was less than proportional to dose. The pharmacokinetics of apatinib in gastric cancer patients were significantly different from those in patients with other cancer types. Dosing of apatinib in various cancer subpopulations may require adjustments to optimize efficacy and benefits to patients.

Indexed as

Administration, OralAdultAgedAntineoplastic AgentsChinaDose-Response Relationship, DrugFemaleHealthy VolunteersHumansMaleMetabolic Clearance RateMiddle AgedModels, BiologicalNeoplasmsProtein Kinase InhibitorsPyridinesAntineoplastic AgentsapatinibProtein Kinase InhibitorsPyridines

Identifiers

PMID27379402
OpenAlexW2467735990

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.