Department of Pharmaceutics & Medicinal Chemistry, T. J. Long School of Pharmacy & Health Sciences, University of the Pacific, Stockton, California 95211, USA.
AAPS PharmSciTech. 2009;10(4):1331-5. doi: 10.1208/s12249-009-9332-0. Epub 2009 Nov 10.
The relative bioavailability of chlorothiazide from mucoadhesive polymeric compacts is compared to commercial oral suspension in pigs. A single-dose randomized study was conducted in 12 healthy pigs that are 9-10 weeks old. After overnight fasting, pigs were divided into two groups of six animals. To the first group, a reference product containing 50 mg of chlorothiazide suspension, and in the second group, test product (mucoadhesive compacts) chlorothiazide (50 mg) was administered with 75 mL of water via gastric tubes. Blood samples were collected between 0 to 24 h using catheters inserted into the jugular vein. Plasma was separated by protein precipitation, and chlorothiazide concentrations were determined using a high-performance liquid chromatography method. The mean Tmax and the Cmax of chlorothiazide following the administration of oral suspension and mucoadhesive compacts were 0.58+/-0.20 h and 682.97+/-415.69 ng/mL and 2.17+/-0.98 h and 99.42+/-124.08 ng/mL, respectively. The Kel and T1/2 of chlorothiazide were found to be 1.06+/-0.28 h(-1) and 0.70+/-0.21 h from suspension and 0.95+/-1.11 h(-1) and 2.05+/-1.90 h from the compacts, respectively. The Tmax of mucoadhesive compacts were significantly longer (p<0.05; 2.17 h) than the reference products (0.58 h), whereas the Cmax of compacts were significantly lower (99 ng/mL) than the reference product (683 ng/mL; p<0.05). The area under the curve (AUC) of compacts accounts only 50.15% (404.32+/-449.93 ng h/mL) of the reference product's AUC (806.27+/-395.97 ng h/mL). The relative bioavailability of the compacts was lower than that of the suspension, and this may be due to the narrow window of absorption for chlorothiazide.
将黏膜粘附聚合物制剂中的氯噻嗪的相对生物利用度与市售口服混悬液进行比较。在 12 头 9-10 周龄的健康猪中进行了一项单剂量随机研究。禁食过夜后，将猪分为两组，每组 6 只。第一组给予含有 50mg 氯噻嗪混悬液的参比制剂，第二组给予含有 50mg 氯噻嗪的试验制剂（黏膜粘附制剂），用 75ml 水通过胃管给药。通过插入颈静脉的导管在 0 至 24 小时之间采集血样。通过蛋白沉淀分离血浆，并使用高效液相色谱法测定氯噻嗪浓度。口服混悬液和黏膜粘附制剂给药后氯噻嗪的平均 Tmax 和 Cmax 分别为 0.58±0.20h 和 682.97±415.69ng/ml 和 2.17±0.98h 和 99.42±124.08ng/ml。氯噻嗪的 Kel 和 T1/2 从混悬液中分别为 1.06±0.28h-1和 0.70±0.21h，从制剂中分别为 0.95±1.11h-1和 2.05±1.90h。黏膜粘附制剂的 Tmax 明显长于参比制剂（2.17h，p<0.05），而制剂的 Cmax 明显低于参比制剂（99ng/ml，p<0.05）。制剂的 AUC 仅占参比产品 AUC（806.27±395.97ng h/ml）的 50.15%（404.32±449.93ng h/ml）。制剂的相对生物利用度低于混悬液，这可能是由于氯噻嗪的吸收窗口较窄。
