Document Type

Article

Publication Date

11-28-2018

Abstract

Treatment of the injured joint with rhPRG4 is based on recent observations that inflammation diminishes expression of native PRG4. Re‐establishing lubrication between pressurized and sliding cartilage surfaces during locomotion promotes the nascent expression of PRG4 and thus intra‐articular (IA) treatment strategies should be supported by pharmacokinetic evidence establishing the residence time of rhPRG4. A total of 21 Yucatan minipigs weighing ∼55 Kg each received 4 mg of 131I‐rhPRG4 delivered by IA injection 5 days following surgical ACL transection. Animals were sequentially euthanized following IA rhPRG4 at 10 mins (time zero), 24, 72 hrs, 6, 13 and 20 days later. The decay of the 131I‐rhPRG4 was measured relative to a non‐injected aliquot and normalized to the weight of cartilage samples, menisci and synovium, and known cartilage volumes from each compartment surface obtained from representative Yucatan minipig knees. Decay of 131I‐rhPRG4 from joint tissues best fit a two‐compartment model with an α half‐life (t1/2α) of 11.28 hours and β half‐life (t1/2β) of 4.81 days. The tibial and femoral cartilage, meniscii and synovium retained 7.7% of dose at 24 hrs. High concentrations of rhPRG4 were found in synovial fluid (SF) that was non‐aspiratable and resided on the articular surfaces, removable by irrigation, at 10 mins following 131I‐rhPRG4 injection. Synovial fluid K21 exceeded K12 and SF t1/2β was 28 days indicating SF is the reservoir for rhPRG4 following IA injection. Clinical Significance: rhPRG4 following IA delivery in a traumatized joint populates articular surfaces for a considerable period and may promote the native expression of PRG4.

Comments

This is the accepted version of the following article:

Hurtig M, Zaghoul I, Sheardown H, et al. A two compartment pharmacokinetic model describes the intra‐articular delivery and retention of rhPRG4 following ACL transection in the Yucatan mini pig. J Orthop Res. 2018. doi: 10.1002/jor.24191

which has been published in final form at DOI: 10.1002/jor.24191. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

Copyright

Wiley

Available for download on Thursday, November 28, 2019

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