Pfizer Inc, Groton, CT, USA.
J Pain Res. 2012;5:401-8. doi: 10.2147/JPR.S35450. Epub 2012 Oct 23.
This study compared the pharmacokinetic profile, and systemic and local absorption of diclofenac, following dermal patch application and oral administration in Yorkshire-Landrace pigs.
Twelve anesthetized, female, Yorkshire-Landrace pigs were randomized to receive either the dermal patch (FLECTOR(®) patch, 10 × 14 cm; Alpharma Pharmaceuticals, a subsidiary of Pfizer Inc, New York, NY) or 50 mg oral diclofenac (Voltaren(®); Novartis, East Hanover, NJ). Tissue (skin area of 2 × 2 cm and underlying muscles approximately 2-3 cm in depth) and blood (10 mL) samples were collected at timed intervals up to 11.5 hours after initial patch application or oral administration. The concentrations of diclofenac in plasma, skin, and muscle samples were analyzed using validated ultra performance liquid chromatography tandem mass spectrometric methods.
Peak systemic exposure of diclofenac was very low by dermal application compared with oral administration (maximum concentration [C(max)] values of 3.5 vs 9640 ng/mL, respectively). Absorption of diclofenac into underlying muscles beneath the dermal patch was sustained, and followed apparently zero-order kinetics, with the skin serving as a depot with elevated concentrations of diclofenac. Concentrations of diclofenac in muscles beneath the patch application site were similar to corresponding tissues after oral administration (C(max) values of 879 and 1160 ng/mL, respectively). In contrast to the wide tissue distribution of diclofenac after oral administration, dermal patch application resulted in high concentrations of diclofenac only on the treated skin and immediate tissue underneath the patch. Low concentrations of diclofenac were observed in the skin and muscles collected from untreated areas contralateral to the site of dermal patch application.
Dermal patch application resulted in low systemic absorption and high tissue penetration of diclofenac compared with oral administration.
本研究比较了双氯芬酸经皮贴剂和口服给药后的药代动力学特征、全身和局部吸收情况。
12 头麻醉的雌性约克夏-兰开夏猪随机分为两组，分别接受皮贴剂（FLECTOR®贴剂，10×14cm；辉瑞制药公司旗下的 Alpharma 制药公司，纽约，NY）或 50mg 口服双氯芬酸（Voltaren®；诺华制药公司，东不伦瑞克，NJ）治疗。在初始贴剂应用或口服给药后 11.5 小时内，以时间间隔采集组织（2×2cm 皮肤面积和大约 2-3cm 深度的下面肌肉）和血液（10mL）样本。使用经验证的超高效液相色谱串联质谱法分析血浆、皮肤和肌肉样本中的双氯芬酸浓度。
与口服给药相比，经皮应用双氯芬酸的全身暴露峰值非常低（最大浓度 [C(max)]值分别为 3.5 和 9640ng/mL）。双氯芬酸向贴剂下方的下面肌肉的吸收是持续的，并且呈现明显的零级动力学，皮肤作为双氯芬酸浓度升高的储存库。贴剂应用部位下面肌肉中的双氯芬酸浓度与口服给药后相应组织相似（C(max)值分别为 879 和 1160ng/mL）。与口服给药后双氯芬酸广泛的组织分布相反，皮贴剂应用仅导致治疗皮肤和贴剂下方的即时组织中双氯芬酸浓度升高。在未治疗的与皮贴剂应用部位相对的区域采集的皮肤和肌肉中，双氯芬酸浓度较低。
与口服给药相比，双氯芬酸经皮贴剂应用导致全身吸收低和组织穿透率高。
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