title: The influence of the time-of-day administration of the drug on the pharmacokinetics of sunitinib in rabbits.
abstract: OBJECTIVE
  At present it is known that the adjustment of the anticancer therapy to the circadian rhythms in tissues reduces the toxicity of the treatment. Chronotherapy also increases the efficacy of the anticancer treatment, which has been proved for many drugs. Sunitinib is a tyrosine kinase inhibitor, which is broadly used for the treatment of numerous cancers. The aim of the study was a comparison of the concentrations and pharmacokinetics of sunitinib after a single administration to rabbits at 08:00 (control group) and 20:00. Additionally, the effect of sunitinib on glucose levels was investigated.
  
  
  METHODS
  The research was carried out on two groups of rabbits: I08:00, a group with the drug administered at 08:00 (n=8) and II20:00, a group with the drug administered at 20:00 (n=8). The rabbits were treated with sunitinib at an oral dose of 25 mg. Plasma concentrations of sunitinib and its metabolite (SU12662) were measured with a validated HPLC method with UV detection.
  
  
  RESULTS
  The comparison of the sunitinib Cmax and AUC0-t in the group with sunitinib administered at 20:00 with the control group gave the ratios of 2.20 (90% confidence interval (CI) (2.17; 2.22) and 1.64 (1.61; 1.68), respectively. Statistically significant differences between the groups under analysis were revealed for Cmax (p < 0.0001), AUC0-t (p = 0.0079), AUC0-∞ (p = 0.0149), and tmax (p = 0.0085). The mean glycemia drop was higher in group I08:00. than in group II20:00 (22.7% vs. 14.3%; p = 0.0622). The glycemia values returned to the initial values in 24 h after the administration of the drug in both groups.
  
  
  CONCLUSIONS
  The research proved a significant influence of the time-of-day administration on the pharmacokinetics of sunitinib.
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Poznan, Poland. szalekedyta@wp.pl.
authors.forename: E
authors.initials: E
authors.lastname: Szałek
authors.forename: A
authors.initials: A
authors.lastname: Karbownik
authors.forename: K
authors.initials: K
authors.lastname: Sobańska
authors.forename: W
authors.initials: W
authors.lastname: Połom
authors.forename: T
authors.initials: T
authors.lastname: Grabowski
authors.forename: A
authors.initials: A
authors.lastname: Wolc
authors.forename: M
authors.initials: M
authors.lastname: Matuszewski
authors.forename: E
authors.initials: E
authors.lastname: Grześkowiak
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D004334:Drug Administration Schedule; D007211:Indoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D011758:Pyrroles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D001786:Blood Glucose; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; C544393:SU 12662; D000077210:Sunitinib