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

Autor: Yuki Otani, Hidefumi Kasai, Yusuke Tanigawara
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: CPT: Pharmacometrics & Systems Pharmacology, Vol 10, Iss 3, Pp 188-198 (2021)
Druh dokumentu: article
ISSN: 2163-8306
DOI: 10.1002/psp4.12587
Popis: 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.
Databáze: Directory of Open Access Journals