Pharmacokinetic study of amoxicillin potassium clavulanate dry suspension in adult healthy Chinese subjects
Objective To observe the pharmacokinetic profile of amoxicillin potassium clavulanate dry suspension(amoxicillin 400 mg with clavulanate 57 mg/5 mL)in fasting and fed states in healthy Chinese subjects.Methods Thirty-six healthy Chinese adult subjects were enrolled in each of the fasting and postprandial trials.A single-dose,randomized,open-ended,two-cycle experimental protocol was used in both groups,in which 10 mL of the test preparation(or the reference preparation),amoxicillin potassium clavulanate,was administered orally with water in each cycle,and venous blood samples were collected for the determination of amoxicillin in human plasma using liquid chromatography-tandem mass spectrometry.The blood concentrations of amoxicillin and potassium clavulanate in human plasma were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS),and the pharmacokinetic(PK)parameters of the two active ingredients in the plasma were analyzed by the non-atrial modeling method using PhoenixWinNonlin 8.2 software.Results The pharmacokinetic parameters of the two main active ingredients were as follows:AUC0_∞ of amoxicillin in the fasting group was(36.81±5.16)μg·mL-1·h;AUC0_twas(36.51±5.10)μg·mL-1·h;Cmax was(13.76±3.13)μg·mL-1;t1/2 was(1.42±0.16)h;tmax was 1.25 h.AUC0-∞ for amoxicillin in the postprandial group was(39.65±5.86)μg·mL-1·h;AUC0-t was(37.43±5.70)μg·mL-1·h;Cmaxwas(8.57±1.70)μg·mL-1,t1/2 was(1.77±0.57)h;tmax was 3.25 h.AUC0-∞ of clavulanic acid in fasting group was(2.54±1.37)μg·mL-1·h;AUC0_t was(4.97±2.05)μg·mL-1·h;Cmax was(2.05±0.87)μg·mL-1;t1/2 was(1.20±0.11)h,tmax was 1.25 h.In the postprandial group clavulanic acid had an AUC0-∞ of(2.54±1.37)μg·mL-1·h;AUC0-twas(2.50±1.36)μg·mL-1·h;Cmaxwas(0.76±0.40)μg·mL-1;t1/2 was(1.13±0.16)h;tmax was 2.50 h.Conclusion Taking the drug after a high-fat,high-calorie diet significantly reduced the rate and extent of clavulanic acid absorption,and had no major effect on the absorption and metabolism of amoxicillin.
amoxicillinclavulanic acidpharmacokineticsliquid chromatography-tandem mass spectrometryhealthy Chinese subjects
万方数据
维普
