Chronopharmacokinetics of erlotinib in tumor-bearing mice / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To investigate the effect of the dosing time on the pharmacokinetics oferlotinib.METHODS Female C57BL mice were contained under standardized 12h light/dark circadianconditions (lights on at 700,off at 1900)for 3 weeks and randomly assigned into six groups.Erlotinibhydrochloride was orally administrated to the mice in each group at 800,1200,1600,2000,2400and 400,respectively.Blood was drawn from the eyeballs of the mice at 12 different time points aftereach administration.The plasma concentration of erlotinib was determined through a high-performanceliquid-chromatographic assay and the parameters were calculated by WinNonlin. RESULTSThe area under curre (AUC)and mean residence time (MRT)of these groups were apparently differ-ent.AUC0 ~24 h and MRT0 ~24 h were the lowest in the 2000 administration group as compared to othergroups (P<0.01 ).Tmax of the 2000,2400 and 400 groups was apparently higher than that of the800 and 1200 groups (P<0.01 ).The clearance of the light phase groups was lower than that of thedark phase groups (P<0.01 ),with the highest in the 2000 group.The peak value of cmax appeared inthe 1200 group and the lowest in the 2000 group (P<0.01 ).CONCLUSION Circadian rhythm playsa critical role in pharmacokinetics of erlotinib in mice.