当前位置： SCI文献检索 > OSTEOARTHRITIS AND CARTILAGE期刊下所有文献 > Sustained efficacy of a single intra-articular dose of FX006 in a rat model of repeated localized knee arthritis.

Sustained efficacy of a single intra-articular dose of FX006 in a rat model of repeated localized knee arthritis.

Abstract：

OBJECTIVE:To evaluate the efficacy of a single intra-articular (IA) dose of FX006, an extended-release formulation of triamcinolone acetonide (TCA) in poly(lactic-co-glycolic acid) (PLGA) microspheres, on the sequelae of repeated episodes of synovitis. DESIGN:Three flares of localized synovitis in the right knee of rats were induced over 4 weeks following a single IA injection of various doses of FX006, Kenalog(®) (TCA immediate release or TCA IR), or vehicle. Gait scores were employed to assess analgesic effect, and the joints were evaluated by histology at the end of the study. TCA plasma concentrations and corticosterone levels were monitored through the study. RESULTS:A single IA dose of 0.28 mg FX006 significantly improved gait scores through all three reactivations. TCA IR at 0.06 mg (providing comparable plasma TCA exposure, 10-fold higher Cmax) demonstrated comparable benefit through the first reactivation only and reduced-to-no efficacy thereafter. Significantly improved histological joint scores were observed with effective doses of FX006 but not with TCA IR. Corticosterone levels were initially decreased following both TCA IR and FX006 treatment, but recovered by Day 14. CONCLUSIONS:In localized, repeated synovitis in rats, sustained release of TCA following a single IA injection of FX006 significantly prolonged analgesia relative to TCA IR and significantly improved histological scores with no adverse effect on the HPA axis. Since synovitis can contribute to the pathophysiology of multiple joint diseases such as osteoarthritis (OA), RA and gout, FX006 may be an important treatment option for these conditions.

journal_name

Osteoarthritis Cartilage

journal_title

Osteoarthritis and cartilage

authors

Kumar A,Bendele AM,Blanks RC,Bodick N

doi

10.1016/j.joca.2014.09.019

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

151-60

issue

1

eissn

1063-4584

issn

1522-9653

pii

S1063-4584(14)01265-5

journal_volume

23

pub_type

杂志文章

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