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Quantitative tracking of inflammatory activity at the peak and trough plasma levels of tofacitinib, a Janus kinase inhibitor, via in vivo 18 F‐FDG PET
Author(s) -
Raychaudhuri Sanchita,
Abria Christine,
Harmany Zachary T.,
Smith Charles M.,
KunduRaychaudhuri Smriti,
Raychaudhuri Siba P.,
Chaudhari Abhijit J.
Publication year - 2019
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/1756-185x.13732
Subject(s) - tofacitinib , medicine , janus kinase inhibitor , in vivo , janus kinase , trough (economics) , cancer research , pharmacology , nuclear medicine , cytokine , rheumatoid arthritis , microbiology and biotechnology , biology , macroeconomics , economics
Purpose To assess the capability of in vivo positron emission tomography (PET) using 18 F‐fluorodeoxyglucose ( 18 F‐FDG) to quantify changes in inflammatory activity in response to tofacitinib, a Janus kinase (JAK) inhibitor, over a timeframe of a few hours to few days in a preclinical model of rheumatoid arthritis (RA). Methods Twenty‐four mice with collagen‐induced arthritis in the following groups were assessed: Group 1, where the changes in PET measures for the extremity joints were evaluated at the peak and trough plasma drug levels after administration of a single dose of tofacitinib (4 hours apart); Group 2, where joint PET measures were assessed before treatment and after 6 days of administration of a daily dose of tofacitinib; and group 3 (controls), where joint PET measures were derived from the same mice, 6 days apart. Results At about peak plasma levels of the drug after a single tofacitinib administration, there was a reduction in PET measures compared to pretreatment values, suggesting decreased inflammatory activity. These measures were equivalent to those obtained after 6 days of daily dosing by tofacitinib. However, PET measures at trough plasma levels of the drug from tofacitinib administration were significantly higher than those at peak plasma drug levels and equivalent to pretreatment measures. There were insignificant changes in PET measures for the control animals. Conclusion 18 F‐FDG PET can detect changes in inflammatory activity occurring in response to the JAK inhibitor tofacitinib: (a) during peak and trough plasma drug levels, that is within mere hours of treatment; and (b) over a span of days.