Evidence map›Paper›PMID 40116970›Full record

ArticleCancer chemotherapy and pharmacology2025

Population pharmacokinetic analysis of bevacizumab in Japanese cancer patients with proteinuria: a prospective cohort study.

Takashi Masuda, Taro Funakoshi, Takahiro Horimatsu, Sho Masui, Daiki Hira, Marin Inoue, Kodai Yajima, Shunsaku Nakagawa, Yasuaki Ikemi, Junzo Hamanishi and 9 more

Abstract read
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Article in Cancer chemotherapy and pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
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

19 authors.

Takashi MasudaDepartment of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan.
Taro FunakoshiDepartment of Medical Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Takahiro HorimatsuDepartment of Medical Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Sho MasuiDepartment of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan.
Daiki HiraDepartment of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan.
Marin InoueDivision of Integrative Clinical Pharmacology, Faculty of Pharmacy, Keio University, 1-5-30 Shiba Koen, Minato-Ku, Tokyo, 105-8512, Japan.
Kodai YajimaDivision of Integrative Clinical Pharmacology, Faculty of Pharmacy, Keio University, 1-5-30 Shiba Koen, Minato-Ku, Tokyo, 105-8512, Japan.
Shunsaku NakagawaDepartment of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan.
Yasuaki IkemiDepartment of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan.
Junzo HamanishiDepartment of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Atsushi TakaiDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Shinya YamamotoDepartment of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Takeshi MatsubaraDepartment of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Masaki MandaiDepartment of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Hiroshi SenoDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Motoko YanagitaDepartment of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Manabu MutoDepartment of Medical Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Tomohiro TeradaDepartment of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan.
Atsushi YonezawaDepartment of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan. ayone@keio.jp.

Funding

Grant-in-Aid for Scientific Research (B) (KAKENHI) 19H03389Grant-in-Aid for Scientific Research (B) (KAKENHI) 23H02649JST SPRING JPMJSP2110
6 · The paper itself

Abstract

purposeBevacizumab (BV) is an effective therapeutic antibody utilized in various cancers. Serum BV concentration can be a factor that potentially affects its therapeutic efficacy. Although proteinuria could affect BV pharmacokinetics, its influence was not evaluated in the previous population pharmacokinetic (PopPK) studies. Because BV can cause proteinuria as an adverse event, the present study aimed to develop a PopPK model in patients with proteinuria and to evaluate the influence of proteinuria on BV pharmacokinetics.

methodsThis prospective cohort study enrolled 70 Japanese cancer patients newly starting BV, and 368 concentration samples from these patients were analyzed. Serum BV concentrations were measured at several time points including at the onset of proteinuria. PopPK analysis was conducted using a non-linear mixed-effects modeling program. A two-compartment model was used to estimate total body clearance (CL).

resultsSerum BV concentrations divided by the dose per body weight and dosing interval tended to be lower in patients with higher urinary protein to creatinine ratio (UPCR). The covariate analysis showed that increasing BV CL was associated with decreasing serum albumin concentration and increasing body weight and UPCR. The simulated median trough concentrations of BV in patients with Common Terminology Criteria for Adverse Events grades 1, 2, and 3 proteinuria were decreased by 12.0%, 20.6%, and 31.5%, respectively, compared to those in patients with grade 0.

conclusionWe successfully established a PopPK model incorporating UPCR to predict serum BV concentrations in patients with proteinuria. Our study provides additional insights to better understand BV pharmacokinetics.

Indexed as

Antineoplastic Agents, ImmunologicalBevacizumabNeoplasmsProteinuriaAdultAgedCohort StudiesEast Asian PeopleFemaleHumansJapanMaleMiddle AgedModels, BiologicalProspective StudiesAntineoplastic Agents, ImmunologicalBevacizumabBevacizumabPopulation pharmacokineticsProteinuriaUrinary protein to creatinine ratio

Identifiers

PMID40116970

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