Studies On Pharmacokinetics And Relative Bioavailability Of Zhenkening Buccal Tablet

Zhenkening buccal tablet belonged to the forth sort of new drug of Chinese traditional medicine which was developed from Zhenkening syrup in pharmacopoeia (2000 edition) by altering its dosage form. In this study, the content of ephedrine hydrochloride (EH) in Zhenkening buccal tablet was determined with the method of HPLC and the limit of its content was established. Furthermore, the method determining the plasma concentration of EH was established and was used to study the pharmacokinetics and relative bioavailability of Zhenkening buccal tablet to confirm the superiority of Zhenkening buccal tablet.The content or plasma concentration of EH was determined with an ion-pair reversed-phase high-performance liquid chromato-graphic method. The separation was performed on a Kromasil C-18 column (5um, 200 mmx4.6mm) with a mobile phase of acetonitrile: water: phosphate(48:52:0.1) containing 4g sodium dodecyl sulfonate and the fractions were detected at 210nm wavelength. The flow rate was 1.0ml/min. The samples were treated by the method of ultrasonic extraction for 30 min with methanol. The method study indicated it could be used for the determination of EH in Zhenkening buccal tablet. The plasma concentration of EH was determined under the conditions of the column of Shim-Pack VP-ODS (5jim, 150 X 4.6mm) and the flow rate of 1.5ml/min, other chromatographic conditions as above. Protein precipitation was accomplished by the addition of methanol. The method study indicated it could be used to determine the plasma concentration of EH.10 batches of Zhenkening buccal tablets were determined and the range of 95% ~ 105% of the mark amount 4mg/tablet was established as the content limit of EH.The pharmacokinetics and relative bioavailability were studiedin rabbits. 16 healthy rabbits were divided into two groups at random, test formulation group and reference formulation group. The former were given Zhenkening buccal tablet while the later were given Zhenkening syrup, and they were given its corresponding blank formulation. The plasma concentration of EH was determined by HPLC method as above to study pharmacokinetics and relative bioavailability of test buccal tablet to its reference syrup.The plasma concentration-time curves of the formulations were both fitted to the first absorption two-compartment model. The main pharmacokinetic parameters of EH in two formulations were tmax 0.25h and 0.75h; Cmax 8.99+1.53mg/L and 4.46+0.87mg/L; Ka 29.84+9.851/h and 1.28+0.20 1/h; AUC0., 14.42 + 2.76mg.L-1.h and 11.47 + 2.34 mg.L-1; AUC0- 17.75 + 3.92 mg.L-1.h and 15.81 + 9.06mg.L-1 h for buccal tablet and syrup respectively . The relative bioavailability of buccal tablet to syrup was 112.32%. Analysis of variance for lnAUC indicated the difference between formulations was not significant (p>0.05). Two one-side test showed t1= 2.3074>t1-0.05(14)=1.761 t2=0.1660