Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Pharmacokinetics, Pharmacodynamics, Modeling & Simulation, ICON Plc, Cary, North Carolina, USA.
CPT Pharmacometrics Syst Pharmacol. 2018 Jan;7(1):34-41. doi: 10.1002/psp4.12264. Epub 2017 Dec 14.
The consumption of asparagus is associated with the production of malodorous urine with considerable interindividual variability (IIV). To characterize the urinary odor kinetics after consumption of asparagus spears, we conducted a study with consenting attendees from two American Society for Clinical Pharmacology and Therapeutics (ASCPT) meetings. Subjects were randomized to eat a specific number of asparagus spears, and then asked to report their urinary odor perception. Eighty-seven subjects were included in the final analysis. A mixed effect proportional odds model was developed that adequately characterized the dose-response relationship. We estimated the half-life of the asparagus effect on malodorous urine to be 4.7 hours (relative standard error (RSE) = 13.2%), and identified a dose-response slope term with good precision (24.3%). Age was found as the predictor of IIV in slope estimates. This study design and tools can be used as a demonstration "crowdsourcing" project for studying population kinetics in organizational and educational settings.
芦笋的食用与具有相当个体间变异性(IIV)的恶臭尿液的产生有关。为了描述食用芦笋后尿液气味的动力学变化,我们在两次美国临床药理学与治疗学学会(ASCPT)会议上进行了一项同意参加者的研究。受试者被随机分配食用特定数量的芦笋,然后被要求报告他们的尿液气味感知。最终分析纳入了 87 名受试者。我们开发了一个混合效应比例优势模型,该模型充分描述了剂量反应关系。我们估计芦笋对恶臭尿液的作用半衰期为 4.7 小时(相对标准误差(RSE)= 13.2%),并确定了一个具有良好精度的剂量反应斜率项(24.3%)。年龄被确定为斜率估计中 IIV 的预测因子。这种研究设计和工具可作为在组织和教育环境中研究人群动力学的示范“众包”项目。