Minimal impact of hepatic and renal impairment on plasma protein binding of lenvatinib, and identification of its major plasma binding protein

Plasma protein binding (PPB) can be different depending on the status of hepatic or renal functions. In this study, the PPB of lenvatinib was determined using equilibrium dialysis in plasma from healthy volunteers and from subjects with mild, moderate, or severe hepatic impairment or renal impairmen...

Full description

Saved in:
Bibliographic Details
Published inBiopharmaceutics & drug disposition Vol. 40; no. 8; pp. 307 - 311
Main Authors Mano, Yuji, Mizuo, Hitoshi
Format Journal Article
LanguageEnglish
Published England Wiley Subscription Services, Inc 01.09.2019
Subjects
Online AccessGet full text
ISSN0142-2782
1099-081X
1099-081X
DOI10.1002/bdd.2204

Cover

More Information
Summary:Plasma protein binding (PPB) can be different depending on the status of hepatic or renal functions. In this study, the PPB of lenvatinib was determined using equilibrium dialysis in plasma from healthy volunteers and from subjects with mild, moderate, or severe hepatic impairment or renal impairment. Plasma from these subjects, fortified with lenvatinib at four concentrations (20, 200, 500, or 1200 ng/ml), was dialysed against phosphate buffered saline (PBS), and then determinations of the total concentrations of lenvatinib in plasma and unbound concentrations in PBS were made. In addition, the binding of lenvatinib was determined in human serum albumin (HSA), α1‐acid glycoprotein (AAG), and human γ‐globulin (HG) in order to identify major binding proteins in human plasma. The PPB of lenvatinib in subjects with HI or RI ranged from 97.5% to 98.2% in hepatic impairment and 98.0% to 98.4% in renal impairment, which was similar to that of healthy volunteers. The binding of lenvatinib to HSA, AAG, and HG was 96.6%–97.1%, 46.4%–69.9%, and 19.1%–23.9%, respectively. These findings suggest that lenvatinib mainly binds to HSA and neither renal nor hepatic impairment impacts the PPB of lenvatinib.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
ObjectType-Article-2
ObjectType-Feature-1
content type line 23
ISSN:0142-2782
1099-081X
1099-081X
DOI:10.1002/bdd.2204