Alan Getgood1, Aad Dhollander1,2, Amanda Malone3, James Price3, James Helliwell3. 1. 1 The University of Western Ontario, London, Ontario, Canada. 2. 2 Department of Orthopaedic Surgery and Traumatology, AZ KLINA, Brasschaat, Belgium. 3. 3 Eupraxia Pharmaceuticals, Victoria, British Columbia, Canada.
Abstract
OBJECTIVE: The objective of this pilot study was to determine time point(s) at which maximum concentration of fluticasone propionate (Cmax) occurs in synovial fluid and plasma in Beagle dog knees after intra-articular injection of EP-104IAR. DESIGN: EP-104IAR is composed of fluticasone propionate drug crystals coated with heat-treated polyvinyl alcohol (PVA) to result in extended release properties. Thirty-two Beagle dogs had an injection of EP-104IAR into the knee joint at 2 different dose levels (0.6 mg and 12 mg). Outcome measures included plasma, synovial fluid, and articular cartilage fluticasone propionate concentrations as well as histological analysis of cartilage and synovium at a variety of time points up to 58 days postdosing. RESULTS: Intra-articular administration of 0.6 and 12 mg EP-104IAR was well tolerated. Early minor abnormalities found on microscopy resolved by the end of the study. There were no quantifiable concentrations of fluticasone propionate in plasma of animals administered 0.6 mg at any of the sampling time points. Highest concentrations in plasma following 12 mg administration occurred 1 day postdose and declined with a half-life of approximately 45 days. Highest concentrations of fluticasone propionate in synovial fluid and cartilage generally occurred 5 days postdose in both dose groups and declined with a half-life of approximately 11 to 14 days. CONCLUSIONS: EP-104IAR is capable of providing a safe and prolonged local exposure to a corticosteroid in the synovial joint while minimizing systemic exposure, with peak exposures occurring within a matter of days after dosing before declining in all tissues in a predictable manner.
OBJECTIVE: The objective of this pilot study was to determine time point(s) at which maximum concentration of fluticasone propionate (Cmax) occurs in synovial fluid and plasma in Beagle dog knees after intra-articular injection of EP-104IAR. DESIGN: EP-104IAR is composed of fluticasone propionate drug crystals coated with heat-treated polyvinyl alcohol (PVA) to result in extended release properties. Thirty-two Beagle dogs had an injection of EP-104IAR into the knee joint at 2 different dose levels (0.6 mg and 12 mg). Outcome measures included plasma, synovial fluid, and articular cartilagefluticasone propionate concentrations as well as histological analysis of cartilage and synovium at a variety of time points up to 58 days postdosing. RESULTS: Intra-articular administration of 0.6 and 12 mg EP-104IAR was well tolerated. Early minor abnormalities found on microscopy resolved by the end of the study. There were no quantifiable concentrations of fluticasone propionate in plasma of animals administered 0.6 mg at any of the sampling time points. Highest concentrations in plasma following 12 mg administration occurred 1 day postdose and declined with a half-life of approximately 45 days. Highest concentrations of fluticasone propionate in synovial fluid and cartilage generally occurred 5 days postdose in both dose groups and declined with a half-life of approximately 11 to 14 days. CONCLUSIONS: EP-104IAR is capable of providing a safe and prolonged local exposure to a corticosteroid in the synovial joint while minimizing systemic exposure, with peak exposures occurring within a matter of days after dosing before declining in all tissues in a predictable manner.
Authors: K M Jordan; N K Arden; M Doherty; B Bannwarth; J W J Bijlsma; P Dieppe; K Gunther; H Hauselmann; G Herrero-Beaumont; P Kaklamanis; S Lohmander; B Leeb; M Lequesne; B Mazieres; E Martin-Mola; K Pavelka; A Pendleton; L Punzi; U Serni; B Swoboda; G Verbruggen; I Zimmerman-Gorska; M Dougados Journal: Ann Rheum Dis Date: 2003-12 Impact factor: 19.103
Authors: Neil Bodick; Joelle Lufkin; Christina Willwerth; Anjali Kumar; James Bolognese; Chris Schoonmaker; Rahul Ballal; David Hunter; Michael Clayman Journal: J Bone Joint Surg Am Date: 2015-06-03 Impact factor: 5.284
Authors: Mohammed F Shamji; Helawe Betre; Virginia B Kraus; Jun Chen; Ashutosh Chilkoti; Rajeswari Pichika; Koichi Masuda; Lori A Setton Journal: Arthritis Rheum Date: 2007-11