PMID- 29024802
OWN - NLM
STAT- MEDLINE
DCOM- 20180813
LR  - 20180912
IS  - 1522-9653 (Electronic)
IS  - 1063-4584 (Linking)
VI  - 26
IP  - 1
DP  - 2018 Jan
TI  - Synovial and systemic pharmacokinetics (PK) of triamcinolone acetonide (TA) 
      following intra-articular (IA) injection of an extended-release microsphere-based 
      formulation (FX006) or standard crystalline suspension in patients with knee 
      osteoarthritis (OA).
PG  - 34-42
LID - S1063-4584(17)31226-8 [pii]
LID - 10.1016/j.joca.2017.10.003 [doi]
AB  - OBJECTIVE: Intra-articular (IA) corticosteroids relieve osteoarthritis (OA) pain, 
      but rapid absorption into systemic circulation may limit efficacy and produce 
      untoward effects. We compared the pharmacokinetics (PK) of IA triamcinolone 
      acetonide (TA) delivered as an extended-release, microsphere-based formulation 
      (FX006) vs a crystalline suspension (TAcs) in knee OA patients. METHOD: This 
      Phase 2 open-label study sequentially enrolled 81 patients who received a single 
      IA injection of FX006 (5 mL, 32 mg delivered dose, N = 63) or TAcs (1 mL, 40 mg, 
      N = 18). Synovial fluid (SF) aspiration was attempted in each patient at baseline 
      and one post-IA-injection visit (FX006: Week 1, Week 6, Week 12, Week 16 or Week 
      20; TAcs: Week 6). Blood was collected at baseline and multiple post-injection 
      times. TA concentrations (validated LC-MS/MS, geometric means (GMs)), PK 
      (non-compartmental analysis models), and adverse events (AEs) were assessed. 
      RESULTS: SF TA concentrations following FX006 were quantifiable through Week 12 
      (pg/mL: 231,328.9 at Week 1; 3590.0 at Week 6; 290.6 at Week 12); post-TAcs, only 
      two of eight patients had quantifiable SF TA at Week 6 (7.7 pg/mL). Following 
      FX006, plasma TA gradually increased to peak (836.4 pg/mL) over 24 h and slowly 
      declined to <110 pg/mL over Weeks 12-20; following TAcs, plasma TA peaked at 4 h 
      (9628.8 pg/mL), decreased to 4991.1 pg/mL at 24 h, and was 149.4 pg/mL at Week 6, 
      the last post-treatment time point assessed. AEs were similar between groups. 
      CONCLUSION: In knee OA patients, microsphere-based TA delivery via a single IA 
      injection prolonged SF joint residency, diminished peak plasma levels, and thus 
      reduced systemic TA exposure relative to TAcs.
CI  - Copyright (c) 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Kraus, V B
AU  - Kraus VB
AD  - Duke University School of Medicine, Durham, NC, USA. Electronic address: 
      kraus004@duke.edu.
FAU - Conaghan, P G
AU  - Conaghan PG
AD  - Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds & 
      NIHR Leeds Biomedical Research Centre, Leeds, UK. Electronic address: 
      p.conaghan@leeds.ac.uk.
FAU - Aazami, H A
AU  - Aazami HA
AD  - Hope Clinical Research, Canoga Park, CA, USA. Electronic address: 
      haazami@hopeclinical.com.
FAU - Mehra, P
AU  - Mehra P
AD  - Artemis Institute for Clinical Research, San Diego, CA, USA. Electronic address: 
      pmehra@artemis-research.com.
FAU - Kivitz, A J
AU  - Kivitz AJ
AD  - Altoona Center for Clinical Research, Duncansville, PA, USA. Electronic address: 
      ajkivitz@yahoo.com.
FAU - Lufkin, J
AU  - Lufkin J
AD  - Flexion Therapeutics, Inc., Burlington, MA, USA. Electronic address: 
      jlufkin@flexiontherapeutics.com.
FAU - Hauben, J
AU  - Hauben J
AD  - Flexion Therapeutics, Inc., Burlington, MA, USA. Electronic address: 
      jhauben@flexiontherapeutics.com.
FAU - Johnson, J R
AU  - Johnson JR
AD  - Summit Analytical, Inc., Cary, NC, USA. Electronic address: 
      jjohnson@summitanalytical.com.
FAU - Bodick, N
AU  - Bodick N
AD  - Flexion Therapeutics, Inc., Burlington, MA, USA. Electronic address: 
      nbodick@flexiontherapeutics.com.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20171009
PL  - England
TA  - Osteoarthritis Cartilage
JT  - Osteoarthritis and cartilage
JID - 9305697
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Delayed-Action Preparations)
RN  - F446C597KA (Triamcinolone Acetonide)
SB  - IM
MH  - Anti-Inflammatory Agents/*administration & dosage/pharmacokinetics
MH  - Crystallization
MH  - Delayed-Action Preparations
MH  - Female
MH  - Humans
MH  - Injections, Intra-Articular
MH  - Male
MH  - Microspheres
MH  - Middle Aged
MH  - Musculoskeletal Pain/prevention & control
MH  - Osteoarthritis, Knee/*drug therapy
MH  - Synovial Fluid/metabolism
MH  - Treatment Outcome
MH  - Triamcinolone Acetonide/*administration & dosage/pharmacokinetics
OTO - NOTNLM
OT  - Corticosteroid
OT  - Intra-articular
OT  - Knee osteoarthritis
OT  - Pharmacokinetics
OT  - Synovium
OT  - Triamcinolone
EDAT- 2017/10/13 06:00
MHDA- 2018/08/14 06:00
CRDT- 2017/10/13 06:00
PHST- 2017/03/10 00:00 [received]
PHST- 2017/08/16 00:00 [revised]
PHST- 2017/10/01 00:00 [accepted]
PHST- 2017/10/13 06:00 [pubmed]
PHST- 2018/08/14 06:00 [medline]
PHST- 2017/10/13 06:00 [entrez]
AID - S1063-4584(17)31226-8 [pii]
AID - 10.1016/j.joca.2017.10.003 [doi]
PST - ppublish
SO  - Osteoarthritis Cartilage. 2018 Jan;26(1):34-42. doi: 10.1016/j.joca.2017.10.003. 
      Epub 2017 Oct 9.