Pharmacokinetics of Nivolumab and Erythropoietin in a Rat Model of Diet-Induced Obesity.

IF 3.5 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Pharmaceutical Research Pub Date : 2025-01-23 DOI:10.1007/s11095-025-03819-1

Yi-Hua Sheng, Celine Park, Yae Eun Chong, Christine Yohn, Anna Siemiątkowska, Katarzyna Kosicka-Noworzyń, Amrit Kaur, Karan Sapra, Luigi Brunetti, Leonid Kagan

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引用次数: 0

Abstract

Purpose: To investigate how obesity affects the pharmacokinetics of biologics in a rat model.

Method: Male Long-Evans rats were fed a high-fat diet from the age of 3 weeks and development of obesity was monitored by measuring body size and composition (fat and lean mass). The animals received nivolumab (1 and 8 mg/kg) or recombinant human erythropoietin (rHuEPO, 1000 IU/kg) by intravenous or subcutaneous injection. Serum samples were collected and analyzed using an enzyme-linked immunosorbent assay (ELISA). Endogenous rat IgG was also measured in the nivolumab study. A standard noncompartmental analysis was performed to calculate pharmacokinetic parameters.

Results: When dosed at mg/kg of total body weight approach, no significant differences in pharmacokinetics of nivolumab and rHuEPO between lean and obese cohorts were observed despite significant differences in the body composition. Subcutaneous bioavailability of nivolumab was inversely dependent on the dose level.

Conclusions: Pharmacokinetic parameters of two biologics tested in this work were not affected by obesity, and mg/kg dosing approach was necessary to achieve equivalent exposure in serum. The results were different from our previous findings of significant effect of obesity on pharmacokinetics of human IgG in rats. Additional studies with other biologics are urgently needed in preclinical and clinical settings.

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.