Terhaag B, le Petit G, Richter K, Rogner M
Pharmazie. 1985 Nov;40(11):784-6.
Five different preparations of diclofenac-suppositories (A, B, C, D, E) are investigated for in vitro liberation (modified paddle method) and for in vivo bioavailability in man (8-12 subjects) in a crossover design. In vitro, the time at which 63.2% of the drug are liberated (tL) is 14, 20, 25, 14 and 3.5 min for the preparations A, B, C, D and E, respectively. The steady state concentrations from the preparations B and C are 51 and 11%, respectively, and lower than for the others. In vivo, the time of the concentration maximum (tmax) in min is (mean +/- S mean): A = 68 +/- 18, B = 72 +/- 9, C = 120 +/- 22, D = 42 +/- 3, E = 24 +/- 0.5. The concentration maximum (cmax) in mumol . l-1 at tmax is (mean +/- S mean): A = 5.9 +/- 0.8, B = 3.9 +/- 0.3, C = 3.1 +/- 0.4, D = 5.7 +/- 0.6, and E = 5.5 +/- 0.8. The area under the curve (AUC) for all the preparations has found to be between 8.7 and 10,6 mumol . h . l-1. There is a significant correlation between the in vitro parameter tL and the in vivo data of tmax and cmax, respectively. In consequence, the invasion behaviour in vivo can be derived from in vitro data for drugs with similar good physicochemical properties as diclofenac-Na.
对五种不同的双氯芬酸栓剂制剂（A、B、C、D、E）进行了体外释放研究（改良桨法），并采用交叉设计对人体（8 - 12名受试者）进行了体内生物利用度研究。在体外，制剂A、B、C、D和E释放63.2%药物的时间（tL）分别为14、20、25、14和3.5分钟。制剂B和C的稳态浓度分别为51%和11%，低于其他制剂。在体内，浓度达最大值的时间（tmax，分钟）为（平均值±标准误）：A = 68 ± 18，B = 72 ± 9，C = 120 ± 22，D = 42 ± 3，E = 24 ± 0.5。在tmax时的最大浓度（cmax，μmol·l⁻¹）为（平均值±标准误）：A = 5.9 ± 0.8，B = 3.9 ± 0.3，C = 3.1 ± 0.4，D = 5.7 ± 0.6，E = 5.5 ± 0.8。所有制剂的曲线下面积（AUC）在8.7至10.6 μmol·h·l⁻¹之间。体外参数tL与体内tmax和cmax数据之间分别存在显著相关性。因此，对于具有与双氯芬酸钠相似良好理化性质的药物，其体内的侵入行为可从体外数据推导得出。
