QT interval prolongation and decreased heart rates after intravenous bolus oxytocin injection in male and female conscious rabbits.

The aim of this study was to evaluate changes in heart rate (HR), QT and RR intervals and corrected QT (QTc) values in conscious male and female New Zealand rabbits which intravenously received oxytocin (OXT) at different dosages. Animals were divided into 6 equal groups: group I (n = 6 male, received 0.75 U OXT per animal); group II (n = 6 male, received 1.5 U OXT per animal); group III (n = 6 male, received 3 U OXT per animal); group IV (n = 6 female, received 0.75 U OXT per animal); group V (n = 6 female, received 1.5 U OXT per animal); group VI (n = 6 female, received 3 U OXT per animal). ECG recording were taken from all animals before injection and then at 2, 4, 6, 8, 10, 15 and 20 min of OXT administration. QT and RR intervals obtained at 2 min of OXT administration were significantly prolonged in all groups (p < 0.05) with one exception that is the 1.5 U OXT injected female group where only QT interval did not change. The prolongation of QT and RR intervals persisted for 20 min in 1.5 U OXT injected male group while only QT interval prolongation was obvious for 20 min in 3 U OXT injected female group as for the other groups the prolonged interval were observed for 8-10 min and then returned to baseline values. Generally, a significant prolongation of QTc was noticed in both male and female rabbits at the 2 and 4 min in all groups and bradycardia was noticed at 2 min of OXT administration in all groups. Heart beats returned to normal values in all groups after 8 min of OXT administration. The change of HR, RR, QT and QTc was gender- but not dose-dependent (p < 0.001). The male rabbits were more sensitive to OXT effect then female rabbits. In conclusion, OXT used in therapeutic dosages decreased heart rate and prolonged QT and QTc intervals. Although cardiovascular effect of OXT are of short duration, its use in patient with risk factors for malignant arrhythmias requires more attention.

The possible protective effect of L-carnitine on tilmicosin-induced cardiotoxicity in mice.

The protective effect of L-carnitine was investigated against tilmicosin-induced cardiotoxic effects including blood creatine kinase (CK), CK-MB, total sialic acid as well as the alterations in glutathione and malondialdehyde concentrations in mice. Thirty-two Balb/C mice were divided into four groups including group 1 (control), group 2 (L-carnitine, s.c., 500 mg/kg for 5 days), group 3 (tilmicosin, s.c., single dose of 75 mg/kg) and group 4 (L-carnitine plus tilmicosin). Serum CK, CK-MB and malondialdehyde (MDA) levels were significantly (P < 0.05) higher in group 3 compared with those of other groups. Total sialic acid level in group 3 was found to be significantly (P < 0.05) higher than that in groups 1 and 2, as well. Contrary to these results, glutathione level in group 3 was found to be significantly (P < 0.05) lower than that in groups 1 and 2. In group 4, serum CK, CK-MB, MDA and total sialic acid levels were found to be significantly (P < 0.05) lower than those in group 3. These results suggest that tilmicosin is cardiotoxic in mice as evidenced by higher total sialic acid, CK and CK-MB. In addition, tilmicosin caused the decrease in glutathione and increase in MDA levels. However, administration of L-carnitine could ameliorate these adverse toxic effects of tilmicosin in mice.

Comparative pharmacokinetics of enrofloxacin and tissue concentrations of parent drug and ciprofloxacin after intramuscular administrations of free and liposome-encapsulated enrofloxacin in rabbits.

Pharmacokinetic properties and tissue concentrations of enrofloxacin and ciprofloxacin were compared after intramuscular (i.m.) administrations of free and liposome-encapsulated enrofloxacin at the dose of 5 mg/kg body weight (bw). Twelve healthy adult New Zealand white rabbits were used in the experiment. Blood samples were obtained at 10, 20, 40, 60 and 90 min and 2, 4, 6, 8 and 12 h and tissue samples were collected 24 h after injection. Concentrations of drugs in serum were determined by high-performance liquid chromatography. Pharmacokinetics were best described by a two-compartment open model. Results indicated that absorption rate was slow, peak concentration was higher (P < 0.05), and the time to peak concentration (tmax congruent with 1.5 h) was significantly longer (P < 0.05) for liposome-encapsulated enrofloxacin (LEE) when compared with free enrofloxacin. Values of elimination half-life (t1/2beta = 12.9 h) and mean residence time (MRT = 17.6 h) of liposome-encapsulated enrofloxacin were longer (P < 0.05) and total clearance (Cl = 0.43 l/h/kg) was lower than those of free form. Moreover, the distribution volume at steady-state (Vd(ss) = 14.4 l/kg) of enrofloxacin administered encapsulated into liposomes was significantly higher (P < 0.05) than that of free enrofloxacin (FE). The tissue levels of enrofloxacin and ciprofloxacin after LEE injection were not different (P > 0.05) from FE. In conclusion, the result of present study suggest that LEE may be a beneficial and valuable formulation in the treatment of infectious diseases caused by sensitive pathogens in animals, providing sustained drug release from injection side and prolonged therapeutic serum concentrations after i.m. administration.