Pharmacokinetics And Relative Bioavailability Of Amlodipine Dispersible Tablets Among Healthy Chinese People

Amlodipine is used to treat hypertension and coronarism diseases. It has good properties of better absorption, higher bioavailability, longer half-time, less side effects than the same group of the drugs. It has been widely used as the first-thearapy drug. There hasn't been seen about amlodipine dispersable tablets at market until now. Amlodipine dispersable tablets were advanced by Shantou Laida pharmaceutical factory. In this paper, we used amlodipine tablets as reference formulation, which were produced by Pfizer Pharmaceutical Lit.Co. Amlodipine dispersable tablets were used as the test formulation, which were produced by Shantou Laida pharmaceutical factory. To guide the clinical use of amlodipine, we conducted the pharmacokinetics and relative bioavailability of amlodipine tablets among healthy Chinese people.ObjectiveTo study the pharmacokinetics and relative bioavailability of amlodipine dispersable tablets in Chinese healthy volunteers.MethodsAn open, randomized and crossover study with two weeks washout interval was performed in 18 healthy volunteers. The reference formulation was manufactured by Pfizer Pharmaceutical Limited Company. The test formulation was manufactured by Shantou Laida pharmaceutical factory. The test and the reference formulation were given to 18 healthy male volunteers in a randomized a crossover study. The interval was 2 weeks. None of the subjects had taken any other drugs for at least 2 weeks before the study and did not take any other drugs during the study. Their normal health status were judged on the basis of a physical examination with screening blood chemistries, including a complete blood count and liver function test, urinalysis and electrocardiogram performed before the study. Volunteers were given medicine with tepid water of 200ml in the morning after an overnight fast and were given standard food of low fat and low protein at 4h after medicine. Venous blood samples (7ml of each) were collected into tubes, before the drug administration and at 1,2,3,4,5,6,7,9,12,24,48,72,96,120h after dosing. The blood plasma were stored at -20℃until analysised. The HPLC method was used to determine concentration of amlodipine. The pharmacokinetic data were disposed with 3P97 program. The area under the curve (AUC) was calculated by the linear trapezoidal method. The data are expressed as mean value±SD. The peak concentration (C_max) and the peak time (T_max) of amlodipine were determined from the respective observed concentration-time data.ResultsIt has been studied the pharmacokinetics of amlodipine in Chinese healthy subjects by using the HPLC method. The results showed that the method was specific and selective. In blood plasma and impurity substance in blood plasma didn't interfere with determination of amlodipine. Obtained linear regressin equation of amlodipine is C=0.0001774A+0.05175(r=0.9998). The lower limit of quantization is 0. 5μg·L^-1, the linear range is 0. 5～10.0μg·L^-1. The recoveries, difference intra-day and inter-day all meet with the examnation of living creature sample.The study showed that the data of the two formulations were fitted to a one-compartment open model in healthy volunteers, the pharmacokinetic parameters of the two formulation were as follow: T_max was(6.9±0.9) h and (6.8±0.7) h, C_max was (6.54±0.89)μg·L^-1 and (6.43±0.91)μg·L^-1,T_1/(2ke) was(38.51±4.57)hand(39.10±2.68) h, AUC₀^t and(351.4±42.1)μg·L^-1 and (344.6±39.5)μg·L^-1, AUC₀^∞was(388.6±51.5)μg·L^-1 and (380.0±39.3)μg·L^-1. Compared with standard reference formulation, the relative bioavailability of amlodipine is (98.2±5.4) % (F₀^t) and (98.3±7.1) %(F₀^∞). C_max, AUC₀^t, AUC₀^∞between the two formulation of amlodipine were analyzed with a statistic analysis of ANOVA and two one-side test statistic analysis. T_max was analyzed with nonprametic statistics. The results showed that the two formulations were bioequivalent.Conclusion1,The standard reference and test formulation of amlodipine are fitted to a one-compartment open model in healthy volunteers.2,The two different formulations of amlodipine are bioequivalent.