Aster-Cephac, Paris, France.
Clin Drug Investig. 2004;24(12):739-47. doi: 10.2165/00044011-200424120-00005.
To compare the systemic bioavailability of two ibuprofen formulations, Pedea((R)) (ibuprofen intravenous [IV] formulation) and Imbun((R)) (ibuprofen intramuscular [IM] formulation) in 18 healthy male volunteers.
Each subject received a 5 mg/kg dose of ibuprofen base as a short 15-minute IV infusion as the Pedea((R)) ibuprofen IV formulation or as the reference Imbun((R)) IM formulation. Concentrations of R- and S-ibuprofen were measured by a validated HPLC method with a lower limit of quantification of 0.100 microg/mL.
A single 5 mg/kg injection of Pedea((R)) was well tolerated. The most frequent adverse event was a mild to moderate burning sensation along the injection vein probably related to the study treatments.The maximum serum concentration (C(max)) of R- and S-ibuprofen ranged from 20 to 35 microg/mL with both formulations. No statistical differences were observed for either C(max) or area under the plasma concentration-time curve (AUC). 90% CIs calculated for C(max) and AUC from time zero to infinity (AUC(infinity)) of R-ibuprofen and S-ibuprofen were included in the bioequivalence range 0.80-1.25. Based on AUC(infinity), the mean (SD) relative bioavailability of Pedea((R)) (ibuprofen IV formulation) versus the Imbun((R)) IM reference formulation was 1.06 (0.17) for R-ibuprofen and 1.05 (0.08) for S-ibuprofen.
This study showed that Pedea((R)) (test formulation) is bioequivalent to Imbun((R)) IM (reference formulation) for both R-ibuprofen and S-ibuprofen. The Imbun((R)) IM formulation (lyophilisate) could be replaced by the Pedea((R)) ready-to-use IV solution. Moreover, these results allow a comparison of safety and efficacy data previously generated with either formulation. Consequently, neonatologists, who previously used the IM formulation intravenously for the treatment of patent ductus arteriosus in preterm infants, will now be able to administer the new ready-to-use IV solution of ibuprofen directly.
比较两种布洛芬制剂（Pedea((R))[静脉内（IV）]布洛芬制剂和 Imbun((R))[肌内（IM）]布洛芬制剂）在 18 名健康男性志愿者中的全身生物利用度。
每位受试者均接受 5mg/kg 剂量的布洛芬碱，作为 Pedea((R)) 布洛芬 IV 制剂或参考 Imbun((R)) IM 制剂的短 15 分钟 IV 输注。采用经验证的 HPLC 法测定 R-和 S-布洛芬的浓度，定量下限为 0.100μg/mL。
单次 5mg/kg 注射 Pedea((R)) 耐受性良好。最常见的不良事件是注射静脉沿线出现轻度至中度烧灼感，可能与研究治疗有关。两种制剂的 R-和 S-布洛芬的最大血清浓度（C(max)）范围为 20 至 35μg/mL。C(max)或从时间零到无穷大的血浆浓度-时间曲线下面积（AUC）均未观察到统计学差异。R-布洛芬和 S-布洛芬的 AUC(无穷大)的 90%置信区间（CI）包含在 0.80-1.25 的生物等效范围内。基于 AUC(无穷大)，Pedea((R))（IV 制剂）与 Imbun((R)) IM 参考制剂的 R-布洛芬和 S-布洛芬的平均（SD）相对生物利用度分别为 1.06（0.17）和 1.05（0.08）。
本研究表明，Pedea((R))（试验制剂）在 R-布洛芬和 S-布洛芬方面与 Imbun((R)) IM（参考制剂）具有生物等效性。Imbun((R)) IM（冻干制剂）可被 Pedea((R)) 即用型 IV 溶液替代。此外，这些结果允许对以前使用任何一种制剂生成的安全性和疗效数据进行比较。因此，先前曾使用 IM 制剂为早产儿治疗动脉导管未闭的新生儿科医生，现在将能够直接给予新的即用型 IV 布洛芬溶液。
