Lek Pharmaceuticals d.d., Sandoz Development Center Slovenia, Verovškova 57, 1526, Ljubljana, Slovenia.
University of Ljubljana, Faculty of Pharmacy, Department of Biopharmaceutics and Pharmacokinetics, Askerceva cesta 7, 1000 Ljubljana, Slovenia.
Pharm Res. 2020 Feb 10;37(3):52. doi: 10.1007/s11095-020-2766-5.
We compared results of in vitro performance testing with results of therapeutic equivalence study for calcipotriol/betamethasone ointment, to evaluate their sensitivity and in vivo relevance.
Different in vitro methods were used to evaluate drug release and permeation from the test and reference ointment. Moreover, 444 psoriasis patients were randomized in the therapeutic equivalence study and the parameters of efficacy and safety were compared with in vitro results.
In vitro release and permeation rate of calcipotriol and betamethasone from the test formulation was higher than from the reference product for all methods used (p ≤ 0.05 for calcipotriol and p < 0.01 for betamethasone). Observed batch-to-batch variability of reference product confirmed high sensitivity and discriminatory power of in vitro methods. Higher release and permeation rate of calcipotriol and betamethasone from test product was reflected in the efficacy assessment (mean response difference 4.78 mPASI percentage points), but the observed difference was within the equivalence margins. Systemic exposure to calcipotriol and betamethasone was similar in both treatment groups.
The results of in vitro experiments rank orderly correlated with the results of clinical study. In vitro methods are more sensitive and highly discriminatory when compared to in vivo performance.
我们比较了钙泊三醇/倍他米松软膏的体外性能测试结果与治疗等效性研究结果，以评估它们的敏感性和体内相关性。
使用不同的体外方法评估了试验和参考软膏中药物的释放和渗透。此外，444 例银屑病患者随机分为治疗等效性研究组，比较了疗效和安全性参数与体外结果。
与参考产品相比，试验制剂中钙泊三醇和倍他米松的体外释放和渗透速率在所有使用的方法中均较高（p≤0.05 为钙泊三醇，p<0.01 为倍他米松）。参考产品的批间变异性证实了体外方法的高灵敏度和区分能力。试验产品中钙泊三醇和倍他米松的释放和渗透速率较高反映在疗效评估中（平均反应差异为 4.78 mPASI 百分点），但观察到的差异在等效范围内。两组治疗中钙泊三醇和倍他米松的全身暴露相似。
体外实验结果与临床研究结果有序相关。与体内性能相比，体外方法更敏感，具有更高的区分能力。
