Evidence map›Paper›PMID 34596967›Full record

ArticleCPT: pharmacometrics & systems pharmacology2021

A quantitative systems pharmacology approach to predict the safe-equivalent dose of doxorubicin in patients with cardiovascular comorbidity.

Lan Sang, Yi Yuan, Ying Zhou, Zhengying Zhou, Muhan Jiang, Xiaoquan Liu, Kun Hao, Hua He

Open access · goldAbstract read
In one paragraph

Article in CPT: pharmacometrics & systems pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.1field-weighted citation impact, top 21% 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

5 citing papers in PubMed, 11 citations in OpenAlex.

  1. Advancing drug development with "Fit-for-Purpose" modeling informed approaches.Journal of pharmacokinetics and pharmacodynamics · 2025
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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 1 country.

Lan SangCenter of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
Yi YuanCenter of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
Ying ZhouDepartment of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Zhengying ZhouCenter of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
Muhan JiangCenter of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
Xiaoquan LiuCenter of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
Kun HaoState Key Laboratory of Natural Medicines, Jiangsu Province Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
Hua HeCenter of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
China Pharmaceutical University · CNState Key Laboratory of Natural MedicineNanchang University · CNNingbo No. 2 Hospital · CN

Funding

111 Incubation Project BC2018024Drug Innovation Major Project 2018ZX09711001Fundamental Research Funds for the Central Universities 2632018ZD10Natural Science Foundation of China 81773826Natural Science Foundation of China 81973391Natural Science Foundation of Jiangxi Province 20181BBG70008
6 · The paper itself

Abstract

Patients with cardiovascular comorbidity are less tolerant to cardiotoxic drugs and should be treated with reduced doses to prevent cardiotoxicity. However, the safe-equivalent dose of antitumor drugs in patients with cardiovascular disease/risk is difficult to predict because they are usually excluded from clinical trials as a result of ethical considerations. In this study, a translational quantitative system pharmacology-pharmacokinetic-pharmacodynamic (QSP-PK-PD) model was developed based on preclinical study to predict the safe-equivalence dose of doxorubicin in patients with or without cardiovascular disease. Virtual clinical trials were conducted to validate the translational QSP-PK-PD model. The model replicated several experimental and clinical observations: the left ventricular ejection fraction (LVEF) was reduced and the left ventricular end-diastolic volume (LVEDV) was elevated in systolic dysfunction rats, the LVEF was preserved and LVEDV reduced in diastolic dysfunction rats, and patients with preexisting cardiovascular disease were more vulnerable to doxorubicin-induced cardiac dysfunction than cardiovascular healthy patients. A parameter sensitivity analysis showed that doxorubicin-induced cardiovascular dysfunction was mainly determined by the sensitivity of cardiomyocytes to cardiotoxic drugs and the baseline value of LVEDV, reflected in LVEF change percentage from the baseline. Blood pressure was the least sensitive factor affecting doxorubicin-induced cardiotoxicity.

Indexed as

Models, BiologicalAnimalsCardiovascular DiseasesComorbidityDose-Response Relationship, DrugDoxorubicinHemodynamicsHumansNeoplasmsNetwork PharmacologyRatsDoxorubicin

Identifiers

PMID34596967
PMCPMC8673998
OpenAlexW3203633128

What OpenQuestion holds

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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.