The influence of the time-of-day administration of the drug on the pharmacokinetics of sunitinib in rabbits

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 \u3c 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

Dead zone for hydrogenation of propylene reaction carried out on commercial catalyst pellets

Heterogeneous catalytic processes have for years been of crucial importance in the chemical industry, while biocatalitic processes have become more and more important. For both types of the processes the existence of zones without reactants were reported. Despite the fact that the dead zone can appear in real processes relatively often, the most important problem in practice is the real size of a dead zone inside a catalyst pellet or the real depth of penetration reagents in a biofilm and this is still unsolved. The knowledge of the parameters and some information about the process can allow improvement in yield, and selectivity, reduce consumption of catalyst by reducing the bed size etc. Presented in this work is a simple method of predicting the size of the inactive core of a uniformly activated catalyst pellet. The method is based on a simple mathematical model of catalyst pellet with inactive pellet centre and experimental investigations

The influence of the time-of-day administration of the drug on the pharmacokinetics of sunitinib in rabbits

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 CONCLUSIONS: The research proved a significant influence of the time-of-day administration on the pharmacokinetics of sunitinib.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.</p