Evidence map›Paper›PMID 38157240›Full record

ArticleTherapeutic advances in drug safety2023

Physiologically based pharmacokinetic modeling of candesartan to predict the exposure in hepatic and renal impairment and elderly populations.

Lingfeng Guo, Xinyu Zhu, Lei Zhang, Yichao Xu

Abstract read
In one paragraph

Article in Therapeutic advances in drug safety, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Lingfeng GuoThe First Affiliated Hospital of Zhejiang University Shengzhou Branch, School of Medicine, Shengzhou, Zhejiang, China.
Xinyu ZhuThe First Affiliated Hospital of Zhejiang University Shengzhou Branch, School of Medicine, Shengzhou, Zhejiang, China.
Lei ZhangDepartment of Pharmacy, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang, China.
Yichao XuCenter of Clinical Pharmacology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang 310009, China.ORCID https://orcid.org/0000-0002-0476-9787

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Candesartan cilexetil is a widely used angiotensin II receptor blocker with minimal adverse effects and high tolerability for the treatment of hypertension. Candesartan is administered orally as the prodrug candesartan cilexetil, which is wholly and swiftly converted to the active metabolite candesartan by carboxylesterase during absorption in the intestinal tract. In populations with renal or hepatic impairment, candesartan's pharmacokinetic (PK) behavior may be altered, necessitating dosage adjustments. Objectives: This study was conducted to examine how the physiologically based PK (PBPK) model characterizes the PKs of candesartan in adult and geriatric populations and to predict the PKs of candesartan in elderly populations with renal and hepatic impairment. Design: After developing PBPK models using the reported physicochemical properties of candesartan and clinical data, these models were validated using data from clinical investigations involving various dose ranges. Methods: Comparing predicted and observed blood concentration data and PK parameters was used to assess the fit performance of the models. Results: Doses should be reduced to approximately 94% of Chinese healthy adults for the Chinese healthy elderly population; approximately 92%, 68%, and 64% of that of the Chinese healthy adult dose in elderly populations with mild, moderate, and severe renal impairment, respectively; and approximately 72%, 71%, and 52% of that of the Chinese healthy adult dose in elderly populations with Child-Pugh-A, Child-Pugh-B, and Child-Pugh-C hepatic impairment, respectively. Conclusion: The results suggest that the PBPK model of candesartan can be utilized to optimize dosage regimens for special populations.

Indexed as

candesartanelderly populationhepatic impairmentphysiologically based pharmacokineticsrenal impairment

Identifiers

PMID38157240
PMCPMC10752084

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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 Socratic graph.