RT Journal Article
SR Electronic
T1 Development of a Gold Nanoparticle–Functionalized Surface Plasmon Resonance Assay for the Sensitive Detection of Monoclonal Antibodies and Its Application in Pharmacokinetics
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1361
OP 1367
DO 10.1124/dmd.119.086249
VO 47
IS 11
A1 Haihong Bai
A1 Mei Yuan
A1 Xiaojing Wang
A1 Xinghe Wang
A1 Jinjing Che
YR 2019
UL http://dmd.aspetjournals.org/content/47/11/1361.abstract
AB As a prominent human therapeutic, therapeutic monoclonal antibodies (mAbs) have attracted increasing attention in the past decade due to their high-targeting specificity, low toxicity, and prolonged efficacy. Systematic pharmacokinetic analysis of mAbs not only largely facilitates the understanding of their biologic functions but also promotes the development of therapeutic drug discovery, early clinical trial implementation, and therapeutic monitoring. However, the extremely complex nature of biomatrices and the especially low dosages of mAbs make their detection in biomatrices and further pharmacokinetic analysis highly challenging. Therefore, a method capable of reliably, quickly, and sensitively quantifying mAbs in biomatrices is urgently needed. In this work, we developed and evaluated an gold nanoparticle–functionalized surface plasmon resonance assay for cetuximab (C225) detection and pharmacokinetic analysis in rhesus monkeys. Combining its advantages of label-free pretreatment and amplified signal response, the lower limit of quantitation of C225 in monkey serum was reduced to 0.0125 μg/ml, and the linear range had an order of magnitude comparable to that of an ELISA-based method. Furthermore, the pharmacokinetics of C225 in rhesus monkeys was studied after intravenous infusions of single doses at 7.5, 24, and 75 mg/kg. The concentration of C225 in monkey serum was detectable after dosing for 720 hours. We believe that this new strategy will be applicable as a general protocol for mAb quantification, pharmacokinetic characteristic determination, and toxicokinetic analysis during drug development.