Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
The Christie NHS Foundation Trust, Manchester, United Kingdom.
Clin Pharmacol Ther. 2018 Apr;103(4):582-590. doi: 10.1002/cpt.875. Epub 2017 Oct 16.
Pembrolizumab and nivolumab are highly selective anti-programmed cell death 1 (PD-1) antibodies approved for the treatment of advanced malignancies. Variable exposure and significant wastage have been associated with body size dosing of monoclonal antibodies (mAbs). The following dosing strategies were evaluated using simulations: body weight, dose banding, fixed dose, and pharmacokinetic (PK)-based methods. The relative cost to body weight dosing for band, fixed 150 mg and 200 mg, and PK-derived strategies were -15%, -25%, + 7%, and -16% for pembrolizumab and -8%, -6%, and -10% for band, fixed, and PK-derived strategies for nivolumab, respectively. Relative to mg/kg doses, the median exposures were -1.0%, -4.6%, + 27.1%, and +3.0% for band, fixed 150 mg, fixed 200 mg, and PK-derived strategies, respectively, for pembrolizumab and -3.1%, + 1.9%, and +1.4% for band, fixed 240 mg, and PK-derived strategies, respectively, for nivolumab. Significant wastage can be reduced by alternative dosing strategies without compromising exposure and efficacy.
派姆单抗和纳武利尤单抗是高度选择性的抗程序性细胞死亡蛋白 1（PD-1）抗体，已被批准用于治疗晚期恶性肿瘤。与单克隆抗体（mAb）的体表面积剂量相关的是可变的暴露和显著的浪费。使用模拟评估了以下给药策略：体重、剂量分组、固定剂量和基于药代动力学（PK）的方法。与体重剂量相比，派姆单抗的分组、固定剂量 150mg 和 200mg 以及 PK 衍生策略的相对成本分别为 -15%、-25%、+7%和-16%；而纳武利尤单抗的分组、固定剂量和 PK 衍生策略的相对成本分别为-8%、-6%和-10%。与 mg/kg 剂量相比，派姆单抗的分组、固定剂量 150mg、固定剂量 200mg 和 PK 衍生策略的中位暴露量分别为-1.0%、-4.6%、+27.1%和+3.0%；而纳武利尤单抗的分组、固定剂量 240mg 和 PK 衍生策略的中位暴露量分别为-3.1%、+1.9%和+1.4%。通过替代给药策略，可以减少显著的浪费，而不会影响暴露量和疗效。
