Tissue Distribution And Pharmacokinetics Of Erythromycin

1.The pharmacokinetics of dirithromycin in miceAn LC-MS/MS method has been developed for determination of erythromycylamine in plasma and tissues of mice.A Restek C₁₈（50×2.1mm,5μm）column with a mobile phase composed of methanol-water-foric acid（80:20:0.5,v/v/v）was used in separation.The biological samples were analysed after liquid-liquid extraction,and the concentration of erythromycylamine was calculated by calibration curve accompanied.There were good linear relationships for erythromycylamine in plasma within the range of 0.05～20.0μg·mL^-1.The intra-day and inter-day precision of QC samples were less than 15%,respectively.The recovery of extraction RSD was less than 15%.There were good linear relationships for erythromycylamine in tissue within the range of 0.10～100.0μg·g^-1.The intra-day and inter-day precision of QC samples were less than 15%,respectively.The recovery of extraction RSD was less than 15%.After an i.g.administration of dirithromycin to mice in low,middle and high doses respectively,erythromycylamine had a maximal plasma concentration at about 5h. Erythromycylamine distributed in tissues rapidly after absorbed into blood.The maximal concentration in every tissue achieved at stomach,lung,small intestine,kidney,liver, spleen and heart in turn.2.The pharmacokinetics and bioequivalence of dirithromycin enteric-pellets granules in humanAn LC-MS/MS method has been established for determination of erythromycylamine in human plasma.There was good linear relationships for erythromycylamine in plasma within the range of 1.0～1000ng·mL^-1.The intra-day and inter-day precision of erythromycylamine QC samples were less than 15%,respectively.The recovery of extraction were all more than 50%.The recovery of extraction RSD was less than 15%.A single oral dose 500mg dirithromycin test and reference preparations were given to 20 healthy volunteers in a randomized cross-over design.Main pharmacokinetic parameters were as following:T_maxwere 5.35±1.04,5.70±1.49 h;C_maxwere 571±300,560±215 ng·mL^-1; t_1/2were 26.6±12.0,25.9±8.82 h;AUC_0-twere 6179±3590,5812±3093 ng·h·mL^-1;AUC_0-∞were 6597±3091,6189±3215 ng·h·mL^-1,respectively.After a single dose,relative bioavailability of dirithromycin were 105.3±22.7%.Test and reference formulations are bioequivalent.