Evidence map›Paper›PMID 38536615›Full record

ArticlePharmaceutical research2024

Quantification of Unencapsulated Drug in Target Tissues Demonstrates Pharmacological Properties and Therapeutic Effects of Liposomal Topotecan (FF-10850).

Toshifumi Kimura, Ken Okada, Yasushi Morohashi, Shun Matsuda, Yukio Kato, Mikinaga Mori, Hiroshi Kato, Takeshi Matsumoto, Susumu Shimoyama

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pharmaceutical research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.7field-weighted citation impact, top 32% 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

0 citing papers in PubMed, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Toshifumi KimuraBio Science & Engineering Laboratories, FUJIFILM Corporation, 577 Ushijima, Kaisei-Machi, Ashigarakami-Gun, Kanagawa, 258-8577, Japan. toshifumi.kimura@fujifilm.com.ORCID http://orcid.org/0009-0000-2917-8900
Ken OkadaBio Science & Engineering Laboratories, FUJIFILM Corporation, 577 Ushijima, Kaisei-Machi, Ashigarakami-Gun, Kanagawa, 258-8577, Japan.
Yasushi MorohashiBio Science & Engineering Laboratories, FUJIFILM Corporation, 577 Ushijima, Kaisei-Machi, Ashigarakami-Gun, Kanagawa, 258-8577, Japan.
Shun MatsudaSafety Evaluation Center, Ecology & Quality Management Division, CSR Division, FUJIFILM Corporation, 210 Nakanuma, Minamiashigara, 250-0193, Kanagawa, Japan.
Yukio KatoFaculty of Pharmacy, Kanazawa University, Kakuma-Machi, Kanazawa, Ishikawa, 920-1192, Japan.
Mikinaga MoriBio Science & Engineering Laboratories, FUJIFILM Corporation, 577 Ushijima, Kaisei-Machi, Ashigarakami-Gun, Kanagawa, 258-8577, Japan.
Hiroshi KatoBio Science & Engineering Laboratories, FUJIFILM Corporation, 577 Ushijima, Kaisei-Machi, Ashigarakami-Gun, Kanagawa, 258-8577, Japan.
Takeshi MatsumotoBio Science & Engineering Laboratories, FUJIFILM Corporation, 577 Ushijima, Kaisei-Machi, Ashigarakami-Gun, Kanagawa, 258-8577, Japan.
Susumu ShimoyamaFUJIFILM Pharmaceuticals U.S.A., Inc, One Broadway, Cambridge, MA, 02142, USA.
Fujifilm (Japan) · JPKanazawa University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeQuantifying unencapsulated drug concentrations in tissues is crucial for understanding the mechanisms underlying the efficacy and safety of liposomal drugs; however, the methodology for this has not been fully established. Herein, we aimed to investigate the enhanced therapeutic potential of a pegylated liposomal formulation of topotecan (FF-10850) by analyzing the concentrations of the unencapsulated drug in target tissues, to guide the improvement of its dosing regimen.

methodsWe developed a method for measuring unencapsulated topotecan concentrations in tumor and bone marrow interstitial fluid (BM-ISF) and applied this method to pharmacokinetic assessments. The ratios of the area under the concentration-time curves (AUCs) between tumor and BM-ISF were calculated for total and unencapsulated topotecan. DNA damage and antitumor effects of FF-10850 or non-liposomal topotecan (TPT) were evaluated in an ES-2 mice xenograft model.

resultsFF-10850 exhibited a much larger AUC ratio between tumor and BM-ISF for unencapsulated topotecan (2.96), but not for total topotecan (0.752), than TPT (0.833). FF-10850 promoted milder DNA damage in the bone marrow than TPT; however, FF-10850 and TPT elicited comparable DNA damage in the tumor. These findings highlight the greater tumor exposure to unencapsulated topotecan and lower bone marrow exposure to FF-10850 than TPT. The dosing regimen was successfully improved based on the kinetics of unencapsulated topotecan and DNA damage.

conclusionsTissue pharmacokinetics of unencapsulated topotecan elucidated the favorable pharmacological properties of FF-10850. Evaluation of tissue exposure to an unencapsulated drug with appropriate pharmacodynamic markers can be valuable in optimizing liposomal drugs and dosing regimens.

Indexed as

Antineoplastic AgentsNeoplasmsAnimalsDisease Models, AnimalHumansLiposomesMiceTopoisomerase I InhibitorsTopotecanAntineoplastic AgentsLiposomesTopoisomerase I InhibitorsTopotecandrug releaseliposomeovarian cancertissue distributiontopotecan

Identifiers

PMID38536615
PMCPMC11024016
OpenAlexW4393220329

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Registered trials

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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.