Pharmacodynamic analysis of hypertension caused by lenvatinib using real-world postmarketing surveillance data

Yuki Otani, Hidefumi Kasai, Yusuke Tanigawara

Research output: Contribution to journalArticlepeer-review

Abstract

Lenvatinib is a tyrosine kinase inhibitor of the vascular endothelial growth factor receptor used against nonoperative thyroid cancer; however, hypertension is a major dose-limiting side effect. In this study, hypertension caused by lenvatinib was described through a novel population pharmacodynamic model using postmarketing surveillance data obtained in Japan. The model consists of two maximum effect model components based on the (1) concentration of lenvatinib in plasma and (2) cumulative area under the curve of lenvatinib. In addition, antihypertensive drug of either an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or calcium channel blocker accounted for by lowering effect on diastolic blood pressure. Based on virtual simulations, the combination of antihypertensive drug and dose adjustment of lenvatinib showed a reduction in the probability of grade greater than or equal to 3 hypertension. The present model provides useful guidance in managing hypertension during treatment with lenvatinib in the real-world setting.

Original languageEnglish
Pages (from-to)188-198
Number of pages11
JournalCPT: Pharmacometrics and Systems Pharmacology
Volume10
Issue number3
DOIs
Publication statusPublished - 2021 Mar

ASJC Scopus subject areas

  • Modelling and Simulation
  • Pharmacology (medical)

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