Pérez-Ramos Laura, Ibarra-Gómez Laura, Lubomirov Rubin, García-Cremades María, Asín-Prieto Eduardo, Fudio Salvador, Zubiaur Pablo
PharmaMar S.A., Clinical Pharmacology Department, Clinical Development, 28770 Madrid, Spain.
Department of Pharmaceutics and Food Technology, School of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain.
Pharmaceutics. 2024 Dec 3;16(12):1548. doi: 10.3390/pharmaceutics16121548.
: Pathophysiological variability in patients with cancer is associated with differences in responses to pharmacotherapy. In this work, we aimed to describe the demographic characteristics and hematological, biochemical, and coagulation variables in a large oncology cohort and to develop, optimize, and provide open access to modeling equations for the estimation of variables potentially relevant in pharmacokinetic modeling. : Using data from 1793 patients with cancer, divided into training ( = 1259) and validation ( = 534) datasets, a modeling network was developed and used to simulate virtual oncology populations. All analyses were conducted in RStudio 4.3.2 Build 494. : The simulation network based on sex, age, biogeographic origin/ethnicity, and tumor type (fixed or primary factors) was successfully validated, able to predict age, height, weight, alpha-1-acid glycoprotein, albumin, hemoglobin, C-reactive protein and lactate dehydrogenase serum levels, platelet-lymphocyte and neutrophil-lymphocyte ratios, and hematocrit. This network was then successfully extrapolated to simulate the laboratory variables of eight oncology populations ( = 1200); only East Asians, Sub-Saharan Africans, Europeans, only males, females, patients with an ECOG performance status equal to 2, and only patients with pancreas cancer or ovarian cancer. : this network constitutes a valuable tool to predict relevant characteristics/variables of patients with cancer, which may be useful in the evaluation and prediction of pharmacokinetics in virtual oncology populations, as well as for model-based optimization of oncology treatments.
癌症患者的病理生理变异性与药物治疗反应的差异有关。在这项研究中,我们旨在描述一个大型肿瘤队列中的人口统计学特征以及血液学、生化和凝血变量,并开发、优化和提供可公开访问的建模方程,以估计药物动力学建模中可能相关的变量。使用来自1793名癌症患者的数据,分为训练集(n = 1259)和验证集(n = 534),开发了一个建模网络并用于模拟虚拟肿瘤人群。所有分析均在RStudio 4.3.2 Build 494中进行。基于性别、年龄、生物地理起源/种族和肿瘤类型(固定或主要因素)的模拟网络得到成功验证,能够预测年龄、身高、体重、α-1-酸性糖蛋白、白蛋白、血红蛋白、C反应蛋白和乳酸脱氢酶血清水平、血小板与淋巴细胞比值和中性粒细胞与淋巴细胞比值以及血细胞比容。然后,该网络成功外推以模拟八个肿瘤人群(n = 1200)的实验室变量;仅东亚人、撒哈拉以南非洲人、欧洲人、仅男性、女性、ECOG体能状态等于2的患者以及仅胰腺癌或卵巢癌患者。该网络构成了一个预测癌症患者相关特征/变量的有价值工具,这可能有助于评估和预测虚拟肿瘤人群中的药代动力学,以及基于模型的肿瘤治疗优化。