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 7:00,off at 19:00)for 3 weeks and randomly assigned into six groups.Erlotinibhydrochloride was orally administrated to the mice in each group at 8:00,12:00,16:00,20:00,24:00and 4:00,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 20:00 administration group as compared to othergroups (P<0.01 ).Tmax of the 20:00,24:00 and 4:00 groups was apparently higher than that of the8:00 and 12:00 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 20:00 group.The peak value of cmax appeared inthe 12:00 group and the lowest in the 20:00 group (P<0.01 ).CONCLUSION Circadian rhythm playsa critical role in pharmacokinetics of erlotinib in mice.