Dong-A Pharmaceutical Co. Ltd., Yongin 446-905.
College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
Biomol Ther (Seoul). 2014 May;22(3):260-6. doi: 10.4062/biomolther.2014.037.
This study evaluated the pharmacokinetic profile and therapeutic efficacy of piroxicam (PX), a long acting non-steroidal anti-inflammatory drug for the treatment of arthritis, following intra-articular (IA) injection in comparison to the pharmacokinetic profile and therapeutic efficacy of PX after intramuscular (IM) injection. In the pharmacokinetic study in rats, systemic exposure and pharmacokinetic parameters of PX after a single IA dose were compared with systemic exposure and pharmacokinetic parameters of PX after administration of the same dose IM (0.6 mg/kg). The anti-inflammatory and analgesic effects of IA PX were evaluated simultaneously in a monoiodoacetate-induced osteoarthritis rat model. The plasma PX concentration rapidly rose following IA injection, and it was comparable to the plasma PX concentration following IM injection, suggesting the rapid efflux of the drug molecule from the joint cavity. However, in the efficacy study, the IA PX administration significantly reduced the knee swelling by reducing the level of prostaglandin E2 in the joint, compared to that following administration of IA vehicle and after administration of the IM PX dose. In addition, we found that the anti-inflammatory and anti-nociceptive efficacies of IA PX were synergistically increased upon co-treatment with hyaluronic acid (HA), a potent agent for the treatment of osteoarthritis, at the weight ratio of 1:1 or 1:2, and these effects were more pronounced than those following administration of HA or PX alone. In conclusion, this study demonstrated the efficacy of the IA use of PX alone and/or in combination with HA in osteoarthritis.
本研究评估了吡罗昔康（PX）的药代动力学特征和治疗效果，作为一种治疗关节炎的长效非甾体抗炎药，与肌肉内（IM）注射后的药代动力学特征和治疗效果进行了比较。在大鼠的药代动力学研究中，比较了单次关节内（IA）给药后 PX 的全身暴露和药代动力学参数与相同剂量 IM（0.6mg/kg）给药后的全身暴露和药代动力学参数。同时，在单碘乙酸诱导的骨关节炎大鼠模型中评估了 IA PX 的抗炎和镇痛效果。IA 注射后，血浆 PX 浓度迅速升高，与 IM 注射后血浆 PX 浓度相当，表明药物分子从关节腔快速流出。然而，在疗效研究中，与 IA 载体给药和 IM PX 剂量给药后相比，IA PX 给药可显著通过降低关节中前列腺素 E2 的水平来减少膝关节肿胀。此外，我们发现，当以 1:1 或 1:2 的重量比与治疗骨关节炎的强效药物透明质酸（HA）联合治疗时，IA PX 的抗炎和镇痛效果协同增强，这些效果比单独使用 HA 或 PX 更明显。总之，本研究证明了 IA 使用 PX 单独和/或与 HA 联合治疗骨关节炎的疗效。
