Duke University School of Medicine, Durham, NC, USA.
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds & NIHR Leeds Biomedical Research Centre, Leeds, UK.
Osteoarthritis Cartilage. 2018 Jan;26(1):34-42. doi: 10.1016/j.joca.2017.10.003. Epub 2017 Oct 9.
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.
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.
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.
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.
关节内（IA）皮质类固醇可缓解骨关节炎（OA）疼痛，但快速吸收到体循环可能会限制疗效并产生不良反应。我们比较了 IA 曲安奈德（TA）的药代动力学（PK），该药物以延长释放的微球制剂（FX006）和结晶悬浮液（TAcs）的形式在膝骨关节炎患者中给药。
这是一项 2 期开放标签研究，连续纳入 81 名接受单次 IA 注射 FX006（5ml，32mg 剂量，N=63）或 TAcs（1ml，40mg，N=18）的患者。在基线和 IA 注射后一次就诊时尝试对每位患者进行滑液抽吸（FX006：第 1 周，第 6 周，第 12 周，第 16 周或第 20 周；TAcs：第 6 周）。在基线和多次注射后采集血液。通过 LC-MS/MS（验证的）测定 TA 浓度（几何平均值（GMs）），PK（非房室分析模型）和不良事件（AE）。
注射 FX006 后，SF TA 浓度可通过第 12 周进行定量（pg/mL：第 1 周为 231,328.9；第 6 周为 3590.0；第 12 周为 290.6）；在 TAcs 后，只有 8 名患者中的 2 名在第 6 周时 SF TA 可定量（7.7pg/mL）。注射 FX006 后，血浆 TA 逐渐增加至 24 小时时达到峰值（836.4pg/mL），并在第 12-20 周缓慢降至<110pg/mL；TAcs 后，血浆 TA 在 4 小时时达到峰值（9628.8pg/mL），在 24 小时时降至 4991.1pg/mL，在第 6 周（最后一次治疗后时间点）为 149.4pg/mL。两组的不良事件相似。
在膝骨关节炎患者中，通过单次 IA 注射微球给药的 TA 可延长 SF 关节驻留时间，降低峰值血浆水平，从而降低与 TAcs 相比的全身 TA 暴露量。
