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A key challenge in the development of central nervous system drugs is the availability of drug target specific blood‐based biomarkers. As a new approach, we applied cluster‐based pharmacokinetic/pharmacodynamic (PK/PD) analysis in brain extracellular fluid (brainECF) and plasma simultaneously after 0, 0.17, and 0.86 mg/kg of the dopamine D2/3 agonist quinpirole (QP) in rats. We measured 76 biogenic amines in plasma and brainECF after single and 8‐day administration, to be analyzed by cluster‐based PK/PD analysis. Multiple concentration‐effect relations were observed with potencies ranging from 0.001–383 nM. Many biomarker responses seem to distribute over the blood‐brain barrier (BBB). Effects were observed for dopamine and glutamate signaling in brainECF, and branched‐chain amino acid metabolism and immune signaling in plasma. Altogether, we showed for the first time how cluster‐based PK/PD could describe a systems‐response across plasma and brain, thereby identifying potential blood‐based biomarkers. This concept is envisioned to provide an important connection between drug discovery and early drug development. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]