The pharmacokinetic interaction between levofloxacin and sunitinib.
BACKGROUND
The aim of this study was to evaluate the impact of sunitinib on pharmacokinetics of levofloxacin. The previous study proved that levofloxacin co-administered with sunitib changes the following pharmacokinetic parameters i.e. Cmax and AUC for both sunitinib and SU012662 (sunitinib metabolite). We will also investigate if the limited sample strategy can be applied for levofloxacin.


METHODS
Rabbits were divided into two groups. In both groups there were six animals. In the control group levofloxacin was administered and in investigated group levofloxacin and sunitinib were co-administered. The dose of levofloxacin was 20mg/kg and the dose of sunitinib was 25mg. The concentration in plasma was determined by HPLC-FLD. The pharmacokinetic parameters were evaluated by WinNonLin software. The results were evaluated by the following statistical tests: Shapiro-Wilk, t-Student and Mann-Whitney test.


RESULTS
Pharmacokinetics of levofloxacin obeys the two-compartment model. Sunitinib influences the following pharmacokinetic parameters of levofloxacin: half-life, elimination constant and volume of distribution. Statistical analysis proved that there is a correlation between AUC and the following five time-points: 0.25 h, 4h, 6h, 10h and 12h.


CONCLUSIONS
The study proved that there is a potential pharmacokinetic interaction between sunitinib and levofloxacin. The statistical analysis proved that the limited sample strategy can be applied for levofloxacin.
Department of Physical Pharmacy and Pharmacokinetics, Poznań University of Medical Sciences, Poznań, Poland. Electronic address: aczyrski@ump.edu.pl.
Andrzej
A
Czyrski
Department of Physical Pharmacy and Pharmacokinetics, Poznań University of Medical Sciences, Poznań, Poland.
Katarzyna
K
Kondys
Department of Clinical Pharmacy and Biopharmacy, Poznań University of Medical Sciences, Poznań, Poland.
Edyta
E
Szałek
Department of Clinical Pharmacy and Biopharmacy, Poznań University of Medical Sciences, Poznań, Poland.
Agnieszka
A
Karbownik
Department of Clinical Pharmacy and Biopharmacy, Poznań University of Medical Sciences, Poznań, Poland.
Edmund
E
Grześkowiak
D000818:Animals; D019540:Area Under Curve; D004347:Drug Interactions / Q000502:physiology; D007211:Indoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D064704:Levofloxacin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D011758:Pyrroles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D000077210:Sunitinib
D007211:Indoles; D011758:Pyrroles; D064704:Levofloxacin; D000077210:Sunitinib
Interaction; Levofloxacin; Limited sample strategy; Sunitinib