Studies On Pharmacokinetics Of Amlodipine And Compound Preparation

Clinically, monotherapy is effective only in 50% patients in achieving optimal blood pressure control. Therefore treatment with two or more antihypertensive drugs belonging to different classes is often necessary. Combination antihypertensive drugs simplify dosing regimens, improve compliance, improve hypertension control, decrease dose-dependent side-effects, and reduce cost as the first-line treatment of hypertension. This work was designed to study the pharmacokinetics of the compound amlodipine and atenolol and compound amlodipine and irbesartan.In the first chapter, six adult healthy dogs in a randomized 2-way crossover study, divided into three groups, were given a single oral dose of compound amlodipine and atenolol (containing 1 mg amlodipine and 50 mg atenolol per tablet, provided by Beijing shuanghe Co. L.), Amlodipine Besylate Tablet (Dalian Huirui Co. L.) and atenolol tablet (Beijing Yimin Co. L.) respectively. The pharmacokinetics and bioequivalence of Amlodipine Besylate Tablet and compound amlodipine and atenolol (represented by amlodipine), atenolol tablet and compound amlodipine and atenolol (represented by atenolol) were compared. The plasma concentrations of amlodipine and atenolol were measured by high performance liquid chromatography. No significant difference appears in the pharmacokinetic parameters between the formulations. The relative bioavailability of compound amlodipine and atenolol (represented by amlodipine) is 97.14%±8.11%. The AUC and C_max between the two formulations, Amlodipine Besylate Tablet and compound amlodipine and atenolol (represented by amlodipine) are bioequivalent. The relative bioavailability of compound amlodipine and atenolol (represented by atenolol) is 108.08%±13.14%. The AUC and C_max between the two formulations, atenolol tablet and compound amlodipine and atenolol (represented by atenolol) are bioequivalent. The results show that the combination of amlodipine and atenolol has not influence each other in pharmacokinetics.In the second chapter, six adult healthy beagle dogs in a randomized 2-way crossover study, divided into three groups, were given a single oral dose of compoundpowder of amiodipine and irbesartan (containing 5 mg amiodipine and 250 mg irbesartan, provided by Jiangsu Hengrui Co. L.), 5 mg amiodipine powder and 250 mg irbesartan powder respectively. The pharmacokinetics and bioequivalence of amiodipine powder and compound amiodipine and irbesartan (represented by amiodipine), irbesartan powder and compound amiodipine and irbesartan (represented by irbesartan) were compared. The plasma concentrations of amiodipine and irbesartan were measured by high performance liquid chromatography-electrospray ionization tandem mass spectrometry. No matrix effect was observed to interfere the peak of amiodipine or irbesartan. The relative recovery of amiodipine and irbesartan were both above 90%. The relative standard deviation of inter- and intra-day of amiodipine and irbesartan were below 10% and 15%, respectively. The lower limit of quantitation of amiodipine and irbesartan in plasma were 4.99 ng/ml and 10.01 ng/ml, with the linear range 4.99-499.00 ng/ml and 10.01-5005.00 ng/ml, respectively. No significant difference appears in the pharmacokinetic parameters between the formulations. The relative bioavailability of compound amiodipine and irbesartan (represented by amiodipine) is 104.06%±14.36%. The AUC and Cmax between the two formulations, amiodipine powder and compound amiodipine and irbesartan (represented by amiodipine) are bioequivalent. The relative bioavailability of compound amiodipine and irbesartan (represented by irbesartan) is 99.70% ± 10.54%. The AUC and Cmax between the two formulations, irbesartan powder and compound amiodipine and irbesartan (represented by irbesartan) are bioequivalent. The results show that the combination of amiodipine and irbesartan has not influence each other in pharmacokinetics.