Pharmacokinetics of oral sustained release clonidine in humans.
Pharmacokinetics of oral sustained release clonidine in humans.
复制标题
口服缓释可乐定在人体中的药代动力学。
作者：
MacGregor Tr;Relihan Gl;Keirns Jj
：在一项交叉研究中，将显示不同体外溶出速率的可乐定片芯（Catapres）与静脉注射可乐定给药，以确定人体体循环吸收速率。对于每种制剂，在所有12名受试者中均获得了极好的生物利用度（0.87-0.96）。当比较标准速释片芯和设计为缓慢溶解的片芯的峰浓度和达峰时间时，存在显著差异（p小于0.05）。使用Loo-Riegelman程序比较口服药代动力学特征与静脉内特征，获得每例受试者中每种制剂的吸收率图。由于从芯的释放被配制为较慢，可乐定的体内吸收速率接近零级输入。将缓释和速释核心组合制成胶囊（Perlonget），得到可预测的吸收速率，使制剂科学家能够控制可乐定口服给药后的血浆水平。可乐定0.2 mg输注后的静脉药代动力学遵循三指数下降，最终相半衰期为13.6 h（调和平均值）。静脉输注后，42.3%的剂量以原型经尿液排泄，肾脏清除率为10.05 +/- 0.65 l/h（167 ml/min）。
: Tablet cores of clonidine (Catapres) showing varying rates of in vitro dissolution were administered in a crossover study with intravenous clonidine to determine the rate of absorption into the systemic circulation in humans. Excellent bioavailability (0.87-0.96) was obtained in all 12 subjects for each of the formulations. When peak concentration and time to peak are compared for the standard immediate release cores and the cores designed to be slowly dissolving there was a significant difference (p less than 0.05). Absorption rate plots for each formulation in each subject were obtained using the Loo-Riegelman procedure of comparing the oral pharmacokinetic profile with the intravenous profile. As the release from the cores were formulated to be slower, the in vivo absorption rate of clonidine approached zero order input. Incorporating combinations of sustained release and immediate release cores into a capsule (Perlonget) gave predictable absorption rates, permitting the formulation scientist to control the plasma levels obtained from oral dosing of clonidine. The intravenous pharmacokinetics of clonidine after a 0.2 mg infusion followed a tri-exponential decline with a final phase half-life of 13.6 h (harmonic mean). Following the intravenous infusion 42.3% of the dose was excreted unchanged in the urine with a renal clearance of 10.05 +/- 0.65 1/h (167 ml/min).