Macía M A, Frias J, Carcas A J, Guerra P, Valiente R, Lucero M L
Clinical Pharmacology Service, Hospital La Paz, Madrid, Spain.
Int J Clin Pharmacol Ther. 1995 Jun;33(6):333-9.
We carried out a comparative study of the bioavailability of a typical, enteric-coated diclofenac with regard to a new dispersible formulation whose faster dissolution results in an earlier onset of its analgesic effect. This randomized, crossover study was conducted in 12 healthy male volunteers, who received in fasting 100 mg of enteric-coated diclofenac (Dolotrén, FAES) and 100 mg of dispersible diclofenac (Dolotrén Dispersable, FAES), with one-week interval between both. Blood samples were taken at pre-established times during the 24 hours after dosing, and plasma concentrations of diclofenac were determined by HPLC. Possible adverse experiences were monitored with a check-list, and blood and urinalysis were performed for safety assessment. The dispersible formulation showed a relative extent of bioavailability between 78% and 99% (90% CI) for the AUC0-infinity, being the 90% CI for the Cmax 63%-129%. The time to Cmax (Tmax) was significantly shorter with the dispersible than with the enteric-coated formulation (95% CI for the difference = 1.5-4.25 hours) as the T0(lag) or time to measurable plasma concentrations (1.9-4.2 hours, 95% CI). A relevant feature in the study was the finding of a second peak at 2-2.5 hours post-dosing in 7 out of 11 profiles of subjects receiving the dispersible formulation. Both formulations were well tolerated in clinical and laboratory terms. In conclusion, the new dispersible formulation of diclofenac allows absorption to begin more rapidly and plasma peak is reached earlier, a fact that may be relevant to the analgesic treatment of acute pain.
我们对一种典型的肠溶包衣双氯芬酸与一种新型可分散片剂的生物利用度进行了比较研究，后者更快的溶解导致其镇痛作用起效更早。这项随机交叉研究在12名健康男性志愿者中进行，他们在空腹状态下分别服用100毫克肠溶包衣双氯芬酸（多洛特伦，法艾斯公司）和100毫克可分散双氯芬酸（多洛特伦分散片，法艾斯公司），两次服药间隔一周。给药后24小时内按照预定时间采集血样，通过高效液相色谱法测定血浆中双氯芬酸的浓度。使用检查表监测可能出现的不良事件，并进行血液和尿液分析以进行安全性评估。对于AUC0至无穷大，可分散片剂的相对生物利用度范围为78%至99%（90%置信区间），Cmax的90%置信区间为63%至129%。与肠溶包衣制剂相比，可分散片剂达到Cmax的时间（Tmax）显著更短（差异的95%置信区间 = 1.5至4.25小时），T0（滞后时间）或达到可测量血浆浓度的时间为1.9至4.2小时（95%置信区间）。该研究的一个相关特征是，在接受可分散片剂的11名受试者的药代动力学曲线中有7条在给药后2至2.5小时出现了第二个峰值。两种制剂在临床和实验室方面耐受性良好。总之，双氯芬酸的新型可分散片剂使吸收开始更快且血浆峰值更早达到，这一事实可能与急性疼痛的镇痛治疗相关。
