Matsuda K, Takaya T, Shimoji F, Muraoka M, Yoshikawa Y, Takada K
Department of Pharmaceutics and Pharmacokinetics, Kyoto Pharmaceutical University, Japan.
J Drug Target. 1996;4(2):59-67. doi: 10.3109/10611869609046263.
The effect of food on the release time of a model drug, fluorescein (FL), has been studied after oral administration to beagle dogs in colon delivery capsule in comparison to conventional gelatin capsule and enteric capsules. The dose of FL was 30 mg for each animal. After oral administration of each test preparation in fasted or postprandial condition (100 grams of commercial solid food was given at 30 min before drug administration), blood samples were collected and plasma FL concentrations were measured spectrofluorometrically. Pharmacokinetic analysis was performed with plasma FL concentration vs. time data and the following parameters were determined; Tmax (the time when plasma FL concentration reaches to its maximum concentration), Cmax (peak plasma FL concentration), Tlag (the time when FL appeared at first into the systemic circulation), AUC (area under the plasma FL concentration vs. Time curve) and MRT (mean residence time). For gelatin capsule, mean Tmax appeared at 0.83 +/- 0.33 (S.E.) h after administration and MRT was 2.67 +/- 0.21 h in fasted condition. By feeding, Tmax and MRT increased to 1.50 +/- 0.76 h and 3.09 +/- 0.49 h. For two enteric HPMCP and Eudragit S capsules, MRT were 2.90 +/- 0.48 h and 5.24 +/- 0.32 h in fasted condition, and 11.30 +/- 1.10 h and 12.83 +/- 0.34 h in postprandial condition, respectively. Tlag also increased by postprandial administration. As colon delivery capsule, time-controlled release capsule (TCC) and two types of intestinal inner pressure-controlled release capsules (PCC) (#1 is a separate type and #2 is a seamless one) were tested. MRT of TCC was 4.76 +/- 0.29 h and 6.43 +/- 0.66 h in fasted and postprandial conditions, respectively. This capsule did not receive the effect of food intake. For #1 PCC, MRTs were 5.32 +/- 0.22 h and 12.28 +/- 0.26 h in fasted and postprandial conditions, respectively. For #2 PCC, MRTs were 5.51 +/- 0.26 h and 13.36 +/- 0.84 h in fasted and postprandial conditions, respectively. In addition, the effect of two times feedings was studied with two PCCs and longer MRTs, 28.44 +/- 1.39 h and 26.32 +/- 1.64 h, were obtained. The release time of FL from PCCs increased by postprandial administration. As compared to the results on two enteric capsules, these PCCs are thought to disintegrate in the colon. However, TCC is thought to disintegrate in the stomach after postprandial administration.
将模型药物荧光素（FL）制成结肠递送胶囊，与传统明胶胶囊和肠溶胶囊相比，研究了食物对其经口给予比格犬后释放时间的影响。每只动物的FL剂量为30毫克。在禁食或餐后状态下（给药前30分钟给予100克市售固体食物）口服每种试验制剂后，采集血样并采用荧光分光光度法测定血浆FL浓度。根据血浆FL浓度与时间的数据进行药代动力学分析，并确定以下参数：Tmax（血浆FL浓度达到最大浓度的时间）、Cmax（血浆FL峰值浓度）、Tlag（FL首次进入体循环的时间）、AUC（血浆FL浓度与时间曲线下的面积）和MRT（平均驻留时间）。对于明胶胶囊，禁食状态下给药后平均Tmax出现在0.83±0.33（标准误）小时，MRT为2.67±0.21小时。进食后，Tmax和MRT分别增加到1.50±0.76小时和3.09±0.49小时。对于两种肠溶羟丙甲纤维素邻苯二甲酸酯（HPMCP）和聚丙烯酸树脂S（Eudragit S）胶囊，禁食状态下MRT分别为2.90±0.48小时和5.24±0.32小时，餐后状态下分别为11.30±1.10小时和12.83±0.34小时。餐后给药Tlag也增加。作为结肠递送胶囊，测试了定时释放胶囊（TCC）和两种类型的肠内压力控制释放胶囊（PCC）（#1为分体式，#2为无缝式）。TCC在禁食和餐后状态下的MRT分别为4.76±0.29小时和6.43±0.66小时。该胶囊未受食物摄入的影响。对于#1 PCC，禁食和餐后状态下的MRT分别为5.32±0.22小时和12.28±0.26小时。对于#2 PCC，禁食和餐后状态下的MRT分别为5.51±0.26小时和13.36±0.84小时。此外，对两种PCC研究了两次进食的影响，获得了更长的MRT，分别为28.44±1.39小时和26.32±1.64小时。餐后给药使PCC中FL的释放时间增加。与两种肠溶胶囊的结果相比，这些PCC被认为在结肠中崩解。然而，TCC被认为在餐后给药后在胃中崩解。
