Zaltoprofen, a propionic acid derivative of non-steroidal anti-inflammatory drugs, has strong inhibitory effects on actue and chronic inflammation. A randomized, dose-escalating study was conducted to evaluate the pha...Zaltoprofen, a propionic acid derivative of non-steroidal anti-inflammatory drugs, has strong inhibitory effects on actue and chronic inflammation. A randomized, dose-escalating study was conducted to evaluate the pharma-cokinetics of single and multiple oral doses of zaltoprofen in 12 healthy Chinese volunteers. Pharmacokinetics was determined from serial blood samples obtained up to 24 h after administration of a single dose of zaltoprofen at 80, 160 or 240 mg and after multiple doses of zaltqorofen at 80 mg 3 times daily. The C max and AUC 0-24 of zaltoprofen were found to be proportional to drug dose. Zaltoprofen was rapidly absorbed （t max =1.46±0.83 h） and cleared （t 1/2 =4.96±2.97 h）. Pharmacokinetic parameters after multiple doses were similar to those after single doses. Zaltoprofen was well tolerated. These results support a tid regimen of zaltoprofen for the management of acute and chronic inflammation.展开更多
Until now, there are no publications about the preformulation studies on(S)-zaltoprofen((S)-ZPF). Hence, we first investigated the solubility of(S)-ZPF, screened solubilizers and performed the pharmacokinetic study of...Until now, there are no publications about the preformulation studies on(S)-zaltoprofen((S)-ZPF). Hence, we first investigated the solubility of(S)-ZPF, screened solubilizers and performed the pharmacokinetic study of(S)-ZPF in the presence of the solubilizers. The measurement of the solubility of(S)-ZPF in 26 different solvents was carried out, including d-alpha tocopheryl polyethylene glycol 1000 succinate(TPGS), 2-hydroxypropyl-β-cyclodextrin(HPCD), and mixtures of individual solvent. The plasma concentration of(S)-ZPF and the amount of(S)-ZPF retained in stomach were determined after oral(35.0 mg/kg) and intravenous(5.0 mg/kg) administration. The solubility of(S)-ZPF showed an increase of 484-fold in TPGS compared to its aqueous solubility. There was a significant increase of AUC 0-24 h for pure(S)-ZPF in the TPGS group(813.59 ± 64.17 μg h/ml) in comparison with AUC 0-24 h in the HPCD group(595.57 ± 71.76 μg h/ml) and water group(465.57 ± 90.89 μg h/ml). In addition, the T max of(S)-ZPF in the TPGS group was 2 h, much faster than that in the HPCD or water groups(5.50 or 5.67 h, respectively). This suggested that TPGS played a significant role in the increase of solubility and bioavailability of(S)-ZPF.展开更多
目的:研究扎托布洛芬片在健康人体的药动学特征。方法:采用Agilent Eclipse Plus C18(150mm×4.6 mm,5μm)色谱柱;甲醇-水(含0.16%冰乙酸,2 m M醋酸铵)(85︰15,v/v)流动相;流速为0.6 m L·min-1;柱温为35℃,血浆样品经沉淀蛋白...目的:研究扎托布洛芬片在健康人体的药动学特征。方法:采用Agilent Eclipse Plus C18(150mm×4.6 mm,5μm)色谱柱;甲醇-水(含0.16%冰乙酸,2 m M醋酸铵)(85︰15,v/v)流动相;流速为0.6 m L·min-1;柱温为35℃,血浆样品经沉淀蛋白质后直接进样。20名健康志愿者分别单次口服80 mg和160 mg后,采用HPLC-MS/MS测定血浆中扎托布洛芬片浓度,并采用Win Non Lin6.2计算药动学参数。结果:单次口服80 mg和160 mg时,主要药动学参数Cmax、Tmax、t1/2分别为(5.00±1.68、9.68±2.53)μg·m L-1、(1.23±0.59、1.75±0.49)h和(3.43±1.60、4.61±2.24)h;AUC(0-t)和AUC(0-∞)分别为(10.52±2.65和19.01±4.22)μg·h·m L-1、(11.05±2.86、19.92±4.50)μg·h·m L-1。结论:本研究测得的药动学参数数据可为扎托布洛芬下一步的临床试验提供有效剂量和安全依据。展开更多
文摘Zaltoprofen, a propionic acid derivative of non-steroidal anti-inflammatory drugs, has strong inhibitory effects on actue and chronic inflammation. A randomized, dose-escalating study was conducted to evaluate the pharma-cokinetics of single and multiple oral doses of zaltoprofen in 12 healthy Chinese volunteers. Pharmacokinetics was determined from serial blood samples obtained up to 24 h after administration of a single dose of zaltoprofen at 80, 160 or 240 mg and after multiple doses of zaltqorofen at 80 mg 3 times daily. The C max and AUC 0-24 of zaltoprofen were found to be proportional to drug dose. Zaltoprofen was rapidly absorbed （t max =1.46±0.83 h） and cleared （t 1/2 =4.96±2.97 h）. Pharmacokinetic parameters after multiple doses were similar to those after single doses. Zaltoprofen was well tolerated. These results support a tid regimen of zaltoprofen for the management of acute and chronic inflammation.
基金supported by the Basic Science Research Program (2016R1A2B4011294) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology
文摘Until now, there are no publications about the preformulation studies on(S)-zaltoprofen((S)-ZPF). Hence, we first investigated the solubility of(S)-ZPF, screened solubilizers and performed the pharmacokinetic study of(S)-ZPF in the presence of the solubilizers. The measurement of the solubility of(S)-ZPF in 26 different solvents was carried out, including d-alpha tocopheryl polyethylene glycol 1000 succinate(TPGS), 2-hydroxypropyl-β-cyclodextrin(HPCD), and mixtures of individual solvent. The plasma concentration of(S)-ZPF and the amount of(S)-ZPF retained in stomach were determined after oral(35.0 mg/kg) and intravenous(5.0 mg/kg) administration. The solubility of(S)-ZPF showed an increase of 484-fold in TPGS compared to its aqueous solubility. There was a significant increase of AUC 0-24 h for pure(S)-ZPF in the TPGS group(813.59 ± 64.17 μg h/ml) in comparison with AUC 0-24 h in the HPCD group(595.57 ± 71.76 μg h/ml) and water group(465.57 ± 90.89 μg h/ml). In addition, the T max of(S)-ZPF in the TPGS group was 2 h, much faster than that in the HPCD or water groups(5.50 or 5.67 h, respectively). This suggested that TPGS played a significant role in the increase of solubility and bioavailability of(S)-ZPF.
文摘目的:研究扎托布洛芬片在健康人体的药动学特征。方法:采用Agilent Eclipse Plus C18(150mm×4.6 mm,5μm)色谱柱;甲醇-水(含0.16%冰乙酸,2 m M醋酸铵)(85︰15,v/v)流动相;流速为0.6 m L·min-1;柱温为35℃,血浆样品经沉淀蛋白质后直接进样。20名健康志愿者分别单次口服80 mg和160 mg后,采用HPLC-MS/MS测定血浆中扎托布洛芬片浓度,并采用Win Non Lin6.2计算药动学参数。结果:单次口服80 mg和160 mg时,主要药动学参数Cmax、Tmax、t1/2分别为(5.00±1.68、9.68±2.53)μg·m L-1、(1.23±0.59、1.75±0.49)h和(3.43±1.60、4.61±2.24)h;AUC(0-t)和AUC(0-∞)分别为(10.52±2.65和19.01±4.22)μg·h·m L-1、(11.05±2.86、19.92±4.50)μg·h·m L-1。结论:本研究测得的药动学参数数据可为扎托布洛芬下一步的临床试验提供有效剂量和安全依据。
