陈宝玲
中国医学科学院阜外医院 神经内科
AIM:To study the pharmacokinetics and relative bioavailability of probucol inclusion complex capsule.METHODS:Following oral administration of a single dose of 250 mg of conventional tablet (formulation A, purchased from the market) and probucol inclusion complex capsule (formulation B, a new formulation for preclinical trial) to each of 6 healthy dogs in a randomized crossover design, the plasma levels of the active drug at different time points were determined by HPLC and the plasma concentration-time profiles of formulation A and B were obtained. The pharmacokinetic parameters as well as relative bioavailability were analyzed.RESULTS:The concentration-time curves of formulation A and formulation B were found to fit a two-compartment open model. The Tmax values of formulation A and formulation B were (9.3 +/- 2.1) h and (9.3 +/- 2.1) h, the Cmax values were (1.5 +/- 1.0) microgram.mL-1 and (2.3 +/- 0.9) microgram.mL-1 and the AUC0-240 values were (85 +/- 56) microgram.h.mL-1 and (134 +/- 55) microgram.h.mL-1, respectively. The relative bioavailability of formulation B was found to be (198 +/- 90)% compared with formulation A. The results of variance analysis and two one-side t-test showed that there was significant difference between the two formulations in the AUC0-240.CONCLUSION:The high bioavailability by the inclusion of formulation B is attributed to the improvement of its water-solubility by the inclusion process and this is supposed to be a key factor for improving drug bioavailability.
Yao xue xue bao = Acta pharmaceutica Sinica 2002
OBJECTIVE:To investigate the effects of higeramine (HG) on hemodynamics and its tolerability and safety so as to see if it can be used in cardiac loading test, and to compare the hemodynamic effects of HG and dobutamine (DB).METHODS:Six dogs were infused intrevenously with HG in escalating doses from l microgram/kg/min through 2 microgram/kg/min and to 4 microgram/kg/min, each dose being given for 5 minutes. Then the dogs were infused intravenously with DB at the escalating doses from 5 microgram/kg/min through 10 microgram/kg/min to 20 microgram/kg/min, each dose being given for 5 minutes. Heart rate (HR), blood pressure (BP), cardiac output (CO), myocardial oxygen consumption (MOC), and coronary blood flow (CBF) were measured at the beginning of test and by the end of each dose-infusion. Electrocardiography was conducted in the meantime. Left ventricular ejection fraction (LVEF) was measured with radionuclide equilibrium ventriculography. Another 8 dogs were given HG at the escalating doses from 1 microgram/kg/min up to 500 microgram/kg/min, each dose being infused for 3 minutes, to observe the tolerability and safety of HG, HR, BP, and ECG were monitored during the test.RESULTS:Intravenous administration of HG results in significant inotropic and chronotropic effects on the heart. HR, MOC, CO and CBF all increased in a dose-dependent manner in both HG and DB tests. HG did not cause significant change in systolic blood pressure (SBP), but a slight decrease in diastolic blood pressure (DBP) was found. HR increased steeply to the peak, and then remained at a plateau level. No significant ECG abnormality was seen except a few occasional premature ventricular beats. No dog died during the study.CONCLUSION:HG can be used in pharmacological stress test with remarkable tolerability and safety even at the dosage of 500 microgram/kg/min without serious adverse effect. It can be used as an alternative agent to DB under appropriate circumstances.
Zhonghua yi xue za zhi 2002
