Augmented Clearance of Nivolumab Is Associated with Renal Functions in Chronic Renal Disease Model Rats

Kazuaki Taguchi, Yukitaka Hayashi, Mayu Ohuchi, Hotaka Yamada, Shigehiro Yagishita, Yuki Enoki, Kazuaki Matsumoto, Akinobu Hamada

研究成果: Article査読

抄録

The clinically approved dose of nivolumab is 240 mg every 2 weeks. However, previous studies have shown that baseline nivolumab clearance (CL) is associated with treatment outcomes in patients with solid cancers, thus motivating researchers to identify prognostic factors and indices influencing nivolumab CL. This study used chronic kidney disease model rats to investigate whether chronic renal impairment affected nivolumab CL and explored the surrogate markers associated with nivolumab CL. We observed that the total CL for nivolumab (CLtot) was approximately 1.42 times higher in chronic kidney disease model rats than that in sham rats with an increased urinary excretion. Additionally, CLtot showed positive correlation with renal CL for nivolumab (CLR) but not with extrarenal CL. Furthermore, the baseline levels of creatinine, blood urea nitrogen, creatinine CL, and urinary albumin/creatine ratio based on laboratory data were also significantly correlated with CLR Our findings suggest that nivolumab CL increases as renal function deteriorates because of an increased excretion of nivolumab in the urine; additionally, laboratory data reflecting renal function may be a feasible index to qualitatively estimate nivolumab CL prior to nivolumab treatment under conditions of renal impairment. SIGNIFICANCE STATEMENT: This study demonstrated that nivolumab was rapidly eliminated from the circulation in chronic kidney disease model rats compared with sham rats with an increased urinary nivolumab excretion. Moreover, nivolumab clearance was significantly correlated with the baseline levels of certain laboratory parameters reflecting renal functions. These results indicate the potential applicability of baseline renal function as a prognostic index to qualitatively estimate nivolumab clearance prior to nivolumab treatment under conditions with renal impairment.

本文言語English
ページ(範囲)822-826
ページ数5
ジャーナルDrug metabolism and disposition: the biological fate of chemicals
50
6
DOI
出版ステータスPublished - 2022 6月 1

ASJC Scopus subject areas

  • 薬理学
  • 薬科学

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