The Pharmacokinetics Of Lovastatin Extended-release Tablets In Human

OBJECTIVESTo establish HPLC electrospray ionization mass spectrometry(HPLC-MS/MS) method for determination of lovastatin in human plasma.And to study the pharmacokinetics of lovastatin extended-release tabletsin human.METHODSA randomed, single blind design with 12 healthy volunteers (sixmale and six female was used in the study). Lovastatin extended-releasetablets were administrated at the dose of 40 mg in the single dose study,and 40 mg daily for 6 days in multiple doses study. Blood samples weretaken after the last dose in both studies at 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0,12.0, 14.0, 16.0, 24.0, 30.0, 36.0, 40.0, 48.0 h, and just before the 4th 5thand 6th dose. Lovastatin plasma concentration was determined byHPLC-MS/MS. The pharmacokinetic parameters were calculated in theSFDA authorized proffesional pharmacokinetic software DAS 2.0statistical analysis was performed by SPSS 11.0.RESULTSThe standard curve was linear in the range of 0.25 to 16μg·L^-1 (r²=0.9981), the relative recovery was from 97% to 107%. The relativestandard deviation (RSD) of interday and intraday assays were both lessthan 10%. The lower limit of quantitation (LLOQ)was 0.25μg·L^-1. The extraction recovery was more than 75%.The main pharmacokinetic parameters (mean±SD) of lovaststin insingle dose study were as follows: T_max was 9.8±2.2 h, C_max was 3.4±1.5μg·L^-1, AUC_0-t was 45.4±14.6μg·h·L^-1, t_1/2 was 7.4±2.3 h, MRT_0-twas 14.3±1.7 h, Vd/F was 63.1±61.3 L·kg^-1.The main pharmacokinetic parameters (mean±SD) of lovaststin inmulti-dose were as follows: C_min was 0.7±0.2μg·L^-1, C_max was 3.2±0.9μg·L^-1, C_ss was 1.7±0.5μg·L^-1, T_max was 8.7±2.0 h, AUC_0-t was 50.7±15.3μg·h·L^-1, V/F was 43.5±52.1 L·kg^-1, T_1/2 was 6.9±1.6 h, MRT_0-twas 14.9±1.7 h, DF was 1.6±0.4. ANOVA analysis was performed, andall the parameters have no difference in gender. The eliminationparameters in single dose and multiple doses studies have no significantdifference.CONCLUSIONSHPLC-MS/MS is a reliable and accurarcy method in determinglovastatin plasma concentration. The lovastatin extended-release tablethas a low degree of fluctuation of plasma concentration. Thepharmacokinetic parameters are similar to that of other race in literature.They are no gender difference and no self inhibit and induce effect inmultiple dose administration. The recommend dose in clinic trial is 40～60mg daily.