Bajaj G, Wang X, Agrawal S, Gupta M, Roy A, Feng Y
Bristol-Myers Squibb, Princeton, New Jersey, USA.
CPT Pharmacometrics Syst Pharmacol. 2017 Jan;6(1):58-66. doi: 10.1002/psp4.12143. Epub 2016 Dec 26.
Nivolumab is a fully human monoclonal antibody that inhibits programmed death-1 activation. The clinical pharmacology profile of nivolumab was analyzed by a population pharmacokinetics model that assessed covariate effects on nivolumab concentrations in 1,895 patients who received 0.3-10.0 mg/kg nivolumab in 11 clinical trials. Nivolumab pharmacokinetics is linear with a time-varying clearance. A full covariate model was developed to assess covariate effects on pharmacokinetic parameters. Nivolumab clearance and volume of distribution increase with body weight. The final model included the effects of baseline performance status (PS), baseline body weight, and baseline estimated glomerular filtration rate (eGFR), sex, and race on clearance, and effects of baseline body weight and sex on volume of distribution in the central compartment. Sex, PS, baseline eGFR, age, race, baseline lactate dehydrogenase, mild hepatic impairment, tumor type, tumor burden, and programmed death ligand-1 expression had a significant but not clinically relevant (<20%) effect on nivolumab clearance.
纳武利尤单抗是一种完全人源化单克隆抗体，可抑制程序性死亡-1激活。纳武利尤单抗的临床药理学特征通过群体药代动力学模型进行分析，该模型评估了11项临床试验中1895例接受0.3-10.0mg/kg纳武利尤单抗患者中协变量对纳武利尤单抗浓度的影响。纳武利尤单抗的药代动力学呈线性，清除率随时间变化。开发了一个完整的协变量模型来评估协变量对药代动力学参数的影响。纳武利尤单抗的清除率和分布容积随体重增加。最终模型纳入了基线体能状态（PS）、基线体重、基线估计肾小球滤过率（eGFR）、性别和种族对清除率的影响，以及基线体重和性别对中央室分布容积的影响。性别、PS、基线eGFR、年龄、种族、基线乳酸脱氢酶、轻度肝功能损害、肿瘤类型、肿瘤负荷和程序性死亡配体-1表达对纳武利尤单抗清除率有显著但无临床意义（<20%）的影响。
