Amlodipine Atorvastatin Statins Bioequivalence Studies

OBJECTIVE：This test is intended to be used for a new era ofShandong Pharmaceutical Co., Ltd. To develop and produce amlodipinebesylate/atorvastatin statins Calcium Dispersible Tablets Pfizerproduction of amlodipine besylate tablets （Norvasc） andatorvastatin calcium （Lipitor）, a mix of medication, stydy humanrelative bioavailability and bioequivalence, the quality of theexamine test preparation drugs.METHODS:According to the twopreparation cycle randomized crossover design50healthyvolunteers were randomly divided into2groups of25each,respectively, oral amlodipine besylate/atorvastatin testformulation and reference formulation （5/10mg）. By highperformance liquid chromatography-tandem mass spectrometry（HPLC/MS/MS） method was used for determination of plasma amlodipineand atorvastatin, adjacent hydroxy atorvastatin blood drugconcentration. Using DAS software processing blood drugconcentration data and calculation parameters, and statisticalanalysis. Medication in the area under the curve （AUC） and the peakconcentration （Cmax） after logarithmic transformation do varianceanalysis and two one side t test and calculate the90%confidenceinterval; Tmax,nonparametric test, making bioequivalenceevaluation to three kinds of preparation. RESULTS: Amlodipine blooddrug concentration of linear range was35～10000pg·mL^-1,the RSDof intra-day was less than5.4%, the RSD of inter-day was less than5%, Low, medium and high recovery rate were91.24%、89.33%and87.57%,The matrix effect were99.69%、88.01%and90.83%;Atorvastain blood drug concentration of linear range was 35～25000pg·mL^-1, the RSD of intra-day was less than6.12%, the RSDof inter-day was less than6.17%, Low, medium and high recovery ratewere77.23%、80.85%and82.69%, The matrix effect were101.25%、99.69%and99.34%； Adjacent hydroxyl atorvastatin blood drugconcentration of linear range was35～10000pg·mL^-1，the RSD ofintra-day was less than10.94%, the RSD of inter-day was less than8.08%, Low, medium and high recovery rate were79.67%、81.96%and76.39%，The matrix effect were97.61%、90.09%and93.43%.The main pharmacokinetic parameters, Which amlodipinepreparations, reference subjects AUC0�'twere （149184.33±56676.23）pg·h·mL^-1and（139195.11±37861.39）pg·h·mL^-1, AUC0�'∞were（157975.76±57544.54）pg·h·mL^-1and （147026.56±40728.31）pg·h·mL^-1；Cmaxwere （3590.70±1812.44）pg·h·mL^-1and （3323.00±1523.44）pg·h·mL^-1；Tmaxwere （8.15±8.02）and（6.72±5.07）h；t1/2were （39.36±8.94）h and （36.82±9.39）h. Atorvastainpreparations, reference subjects AUC0�'twere （25593.34±12746.83）pg·h·mL^-1、（25132.78±12341.03）pg·h·mL^-1；AUC0�'∞were （28942.21±21492.77）pg·h·mL^-1and （28736.58±21102.63）pg·h·mL^-1；Cmaxwere（2810.56±1799.86）pg·h·mL^-1and （3006.80±1819.04）pg·h·mL^-1；Tmaxwere（1.29±1.42）h and（1.21±1.47）h；t1/2were（14.01±6.73）h and （16.44±12.87）h. Adjacent hydroxylatorvastatin AUC0�'twere （31306.61±16876.16）pg·h·mL^-1and（30652.46±18468.14）pg·h·mL^-1；AUC0�'∞were（33223.49±17849.24）pg·h·mL^-1and（32637.61±20132.79）pg·h·mL^-1；Cmaxwere（1885.42±940.97）pg·h·mL^-1and （1872.12±1064.37）pg·h·mL^-1；Tmaxwere（5.15±2.80）h and （5.08±2.68）；t1/2were（10.60±3.04）h and（10.71±3.45）h.With amlodipine and atorvastatin, adjacent atorvastatin AUC0�'tcalculate bioavailability, a preparation of relative biological measurements were （108.63+32.80）%、（114.19+71.18）%and（109.84+40.81）%.CONCLUSION: Statistical inspection results showed that thepreparation has the bioequivalence between test and reference.