The effect of sunitinib on the plasma exposure of intravenous paracetamol and its major metabolite: paracetamol glucuronide.

The study aimed to examine the effect of sunitinib on the plasma exposure of intravenous paracetamol and its major metabolite, paracetamol glucuronide. Both drugs share metabolic pathways in the liver, and the drug interactions between sunitinib and paracetamol administered in higher doses were reported. These interactions resulted in hepatotoxicity. The adult New Zealand male rabbits were divided into three groups (6 animals each): rabbits receiving sunitinib and paracetamol (SUN + PC), rabbits receiving sunitinib (SUN), and a control group receiving paracetamol (PC). Sunitinib was administered orally (25 mg) and paracetamol was administrated intravenously (35 mg/kg). Blood samples for sunitinib and SU12662 assays were collected up to 96 h after drug administration and for paracetamol and paracetamol glucuronide up to 300 min after drug administration. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin were analysed before and after drug administration. A number of pharmacokinetic parameters were analysed. There were no differences in the levels of AST, ALT, and bilirubin among the groups at either time point. Significantly higher values of AUC0-t , AUC0-∞ , and C max and lower clearance and volume of distribution of paracetamol were observed in group PC vs. group SUN + PC (p < 0.01). The maximum plasma concentration of paracetamol glucuronide tended to be higher in group PC 213.27 µg/mL (90 % CI 1.06, 1.25; p = 0.0267). Statistically significant differences were revealed for paracetamol glucuronide mean residence time (MRT); MRT was higher in group SUN + PC than in group PC (p = 0.0375). The mean t max of paracetamol glucuronide was similar in both groups: SUN + PC and group PC (15 and 20 min, respectively). The mean t max of sunitinib was different in groups SUN + PC and SUN (10.0 and 7.0, respectively; p = 0.0134). At the studied doses, neither of the drugs, whether administered alone or together, had hepatotoxic effects. The present study was not able to confirm that sunitinib, administered at low doses in conjunction with paracetamol, displays a hepatoprotective effect. Significant differences were observed in some pharmacokinetic parameters of paracetamol.

[Changes in tracheal ciliated epithelium of rats exposed to environmental tobacco smoke--experimental studies]. / Zmiany w nablonku migawkowym tchawicy szczurów pod wplywem ekspozycji na dym tytoniowy--badania doswiadczalne.

It has been already proved in many experimental studies that tobacco smoke has multiple toxic effects on respiratory tract cells. Alterations in ciliary epithelium of rats trachea after short exposition to high tobacco smoke concentrations in inhaled air were been determinate in current study. Morphological evaluation revealed in lining epithelium voluminous exudate located between epithelium and lamina propria cells with evidently larger number of mast cells.

[Structural changes in tracheal epithelium in environmental smoke exposed rats--experimental studies]. / Zaburzenia struktury nablonka tchawicy u szczurów poddanych ekspozycji na dym tytoniowy w srodowisku--badania doswiadczalne.

It has been already proved in many experimental studies that tobacco smoke has multiple toxic effects on respiratory tract cells. Alterations in cilliary epithelium of rats trachea after short exposition to high tobacco smoke concentrations in inhaled air were been determined in current study. Morphological evaluation revealed in lining epithelium decrease in number of cilliary cells and increase in number of goblet cells. The mucous membrane was thickened and infiltrated with inflammatory cells.