Campus Units

Animal Science

Document Type

Article

Publication Version

Published Version

Publication Date

2014

Journal or Book Title

European Review for Medical and Pharmacological Sciences

Volume

18

Issue

16

First Page

2393

Last Page

2399

Abstract

OBJECTIVES: 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.

MATERIALS AND 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.

Comments

This article is published as Szałek, E., A. Karbownik, K. Sobańska, W. Połom, T. Grabowski, A. Wolc, M. Matuszewski, and E. Grześkowiak. "The influence of the time-of-day administration of the drug on the pharmacokinetics of sunitinib in rabbits." Eur Rev Med Pharmacol Sci 18, no. 16 (2014): 2393-2399.

Copyright Owner

European Review for Medical and Pharmacological Sciences

Language

en

File Format

application/pdf

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