Bioequivalence and safety of lopinavir-ritonavir tablets in healthy Chinese subjects
Objective:To evaluate the bioequivalence and safety of domestic(test)and imported lopinavir-ritonavir tablets(reference)under fasting condition.Methods:A single-center,randomized,open,two-sequence,cross-over design was used.The concentrations of lopinavir-ritonavir or reference preparation 400 mg/100 mg in human plasma were determined by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).The main pharmacokinetic parameters were calculated using Phoenix WinNonlin 8.3.3 and the bioequivalence were evaluated.Results:The geometric mean ratios(90%confidence intervals)of Cmax,AUC0～t and AUC0～∞ of lopinavir of test preparation and reference preparation were 104.58%(101.24%,108.03%),104.77%(100.08%,109.69%),and104.94%(100.54%,109.53%),respectively,and the confidence intervals fell between the equivalence threshold(80%～125%).The SWR of Cmax,AUC0～t and AUC0～∞ of ritonavir in reference preparation were 0.281 3,0.229 4 and 0.225 8,respectively,all were less than 0.294(intra-individual CV%<30%),so the mean bioequivalence method(ABE)was used to evaluate ritonavir.The geometric mean ratios(90%confidence intervals)of Cmax,AUC0～t and AUC0～∞ of ritonavir of the test preparation and the reference preparation were 105.79%(99.12%,112.91%),104.03%(98.75%,109.58%),and 103.62%(98.50%,109.01%),respectively,and the confidence intervals fell between the equivalence threshold(80%～125%).Conclusion:The bioequivalence of the Cmax,AUC0～t and AUC0～∞ of lopinavir and ritonavir in test and reference preparations are valid in fasting state,and the safety and tolerability are good.
lopinavir-ritonavirChinese healthy subjectson an empty stomachpharmacokineticsbioequivalence
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