AIM： To evaluate the bioequivalence of ranitidine and bismuth derived from two compound preparations. METHODS： The bioavailability was measured in 20 healthy male Chinese volunteers following a single oral dose （eq...AIM： To evaluate the bioequivalence of ranitidine and bismuth derived from two compound preparations. METHODS： The bioavailability was measured in 20 healthy male Chinese volunteers following a single oral dose （equivalent to 200 mg of ranitidine and 220 mg of bismuth） of the test or reference products in the fasting state. Then blood samples were collected for 24 h. Plasma concentrations of ranitidine and bismuth were analyzed by high-performance liquid chromatography and inductively coupled plasma-mass spectrometry （ICPMS）, respectively. The non-compartmental method was used for pharmacokinetic analysis. Log-transformed Cmax, AUC（0-t） and AUC（0-∞） were tested for bioequivalence using ANOVA and Schuirmann two-one sided t-test. Tmax was analyzed by Wilcoxon＇s test. RESULTS： Various pharmacokinetic parameters of ranitidine derived from the two compound preparations, including Cmax, AUC（0-t）, AUC（0-∞）, Tmax and T1/2, were nearly consistent with previous observations. These parameters derived from test and reference drug were as follows： Cmax（0.67 ± 0.21 vs 0.68 ± 0.22 mg/L）, AUC（0-t）（3.1 ± 0.6 vs 3.0 ± 0.7 mg/L per hour）, AUC（0-∞）（3.3 ± 0.6 vs 3.2 ± 0.8 mg/L per hour）, Tmax （2.3 ± 0.9 VS 2.1 ± 0.9 h） and T1/2 （2.8 ± 0.3 vs 3.1 ± 0.4 h）. In addition, double-peak absorption profiles of ranitidine were found in some Chinese volunteers. For bismuth, those parameters derived from test and reference drug were as follows： Cmax （11.80 ± 7.36 vs 11.40 ± 6.55 μg/L）, AUC（0-t） （46.65 ± 16.97 vs 47.03 ± 21.49 μg/L per hour）, Tmax （0.50 ± 0.20 vs 0.50 ± 0.20 h） and T1/2 （10.2 ± 2.3 vs 13.0 ± 6.9 h）. Ninety percent of confidence intervals for the test/reference ratio of Cmax, AUC（0-t） and AUC（0-∞） derived from both ranitidine and bismuth were found within the bioequivalence acceptable range of 80%-125%. No significant difference was found in Tmax derived from both ranitidine and bismuth. CONCLUSION： The two compound preparations are bioequivalent and may be prescribed interchangeably.展开更多
文摘AIM： To evaluate the bioequivalence of ranitidine and bismuth derived from two compound preparations. METHODS： The bioavailability was measured in 20 healthy male Chinese volunteers following a single oral dose （equivalent to 200 mg of ranitidine and 220 mg of bismuth） of the test or reference products in the fasting state. Then blood samples were collected for 24 h. Plasma concentrations of ranitidine and bismuth were analyzed by high-performance liquid chromatography and inductively coupled plasma-mass spectrometry （ICPMS）, respectively. The non-compartmental method was used for pharmacokinetic analysis. Log-transformed Cmax, AUC（0-t） and AUC（0-∞） were tested for bioequivalence using ANOVA and Schuirmann two-one sided t-test. Tmax was analyzed by Wilcoxon＇s test. RESULTS： Various pharmacokinetic parameters of ranitidine derived from the two compound preparations, including Cmax, AUC（0-t）, AUC（0-∞）, Tmax and T1/2, were nearly consistent with previous observations. These parameters derived from test and reference drug were as follows： Cmax（0.67 ± 0.21 vs 0.68 ± 0.22 mg/L）, AUC（0-t）（3.1 ± 0.6 vs 3.0 ± 0.7 mg/L per hour）, AUC（0-∞）（3.3 ± 0.6 vs 3.2 ± 0.8 mg/L per hour）, Tmax （2.3 ± 0.9 VS 2.1 ± 0.9 h） and T1/2 （2.8 ± 0.3 vs 3.1 ± 0.4 h）. In addition, double-peak absorption profiles of ranitidine were found in some Chinese volunteers. For bismuth, those parameters derived from test and reference drug were as follows： Cmax （11.80 ± 7.36 vs 11.40 ± 6.55 μg/L）, AUC（0-t） （46.65 ± 16.97 vs 47.03 ± 21.49 μg/L per hour）, Tmax （0.50 ± 0.20 vs 0.50 ± 0.20 h） and T1/2 （10.2 ± 2.3 vs 13.0 ± 6.9 h）. Ninety percent of confidence intervals for the test/reference ratio of Cmax, AUC（0-t） and AUC（0-∞） derived from both ranitidine and bismuth were found within the bioequivalence acceptable range of 80%-125%. No significant difference was found in Tmax derived from both ranitidine and bismuth. CONCLUSION： The two compound preparations are bioequivalent and may be prescribed interchangeably.
