title: Chronopharmacokinetics of Erlotinib and Circadian Rhythms of Related Metabolic Enzymes in Lewis Tumor-Bearing Mice.
abstract: OBJECTIVE
  The purpose of the current study was to investigate the effect of the dosing time on the pharmacokinetics of erlotinib and the circadian rhythms of the metabolism enzymes in tumor-bearing mice.
  
  
  METHODS
  Female C57BL mice were randomly assigned to six groups. Erlotinib was orally administrated to the mice in each group at six different times of day. The plasma concentration of erlotinib was determined through a high-performance liquid-chromatographic assay, and the total mRNA was extracted from liver tissues to determine the expression of the mRNA of the related drug metabolism enzymes by qRT-PCR.
  
  
  RESULTS
  The results indicated that AUC0-24 h and MRT0-24 h were the lowest in the 20:00 group (P < 0.01). T max of the 13 HALO (hour after light onset), 17 HALO and 21 HALO groups was higher than that of the 1 HALO and 5 HALO groups (P < 0.01). CL of the light-phase groups was lower than that of the dark-phase groups (P < 0.01). The peak value of C max appeared in the 5 HALO group (P < 0.01). The mRNA levels of Cyp3a11, Cyp3a13 and Cyp1a2 were generally higher during the afternoon and the dark phase.
  
  
  CONCLUSIONS
  Circadian rhythm plays a critical role in the pharmacokinetics of erlotinib in mice, and the mechanisms may be attributed to gene expression rhythms of drug-metabolizing enzymes in liver tissues.
authors.affiliation: Department of Pharmacy, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, No. 401 Hospital of Chinese People's Liberation Army, Qingdao, Shandong, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, No. 401 Hospital of Chinese People's Liberation Army, Qingdao, Shandong, China.
authors.forename: Song-Gang
authors.initials: SG
authors.lastname: Ji
authors.affiliation: Department of Pharmacy, No. 401 Hospital of Chinese People's Liberation Army, Qingdao, Shandong, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Wang
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, No. 401 Hospital of Chinese People's Liberation Army, Qingdao, Shandong, China.
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, Medical College of Qingdao University, Qingdao, Shandong, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Medical College of Qingdao University, Qingdao, Shandong, China.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Lin
authors.affiliation: Weifang Institute of Dermatology, Weifang, Shandong, China.
authors.forename: Le-Kun
authors.initials: LK
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, No. 401 Hospital of Chinese People's Liberation Army, Qingdao, Shandong, China. lmc401y@163.com.
authors.forename: Ming-Chun
authors.initials: MC
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000067573:Chronopharmacokinetics; D002940:Circadian Rhythm / Q000502:physiology*; D000069347:Erlotinib Hydrochloride / Q000378:metabolism* / Q000493:pharmacokinetics*; D005260:Female; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D000069347:Erlotinib Hydrochloride