A comparative pharmacokinetic study of a novel sustained release danofloxacin formulation and the conventional product in rabbits.

Sustained release drug formulations are frequently developed to reduce dosage frequency and to improve outcomes of drug therapy. This study evaluates the pharmacokinetic (PK) parameters of a novel injectable danofloxacin (DANO) formulation in comparison with a conventional product in an animal model. A recently synthesized DANO formulation, prepared by incorporation of DANO-loaded mesoporous silica nanoparticles in liposomes and integration of liposomes in chitosan and ß-glycerophosphate solution (lipogel) along with the conventional DANO product were injected subcutaneously (SC) in rabbits. Blood samples were collected at specific time points and DANO concentrations in plasma samples were measured. The PK parameters including maximum concentration (Cmax), time to reach Cmax (Tmax), area under the concentration versus time curves (AUC), area under the first moment concentration-time curve (AUMC) and mean residence time (MRT) were studied by non-compartmental analyses. The values of MRT (156.00 ± 20.00 hr), AUC (15.30 ± 3.00 µg mL-1 per hr) and Tmax (4.70 ± 1.60 hr) for lipogel formulation were higher than those of the conventional product (8.50 ± 3.60 hr, 3.70 ± 2.00 µg mL-1 per hr and 0.80 ± 0.26 hr, respectively). However, Cmax values for lipogel formulation (0.41 ± 0.15 µg mL-1) were significantly lower than those of the conventional drug product (0.68 ± 0.09 µg mL-1). It was concluded that the novel DANO lipogel effectively slowed down the drug absorption and the incorporation of liposomes in hydrogel could be a useful approach to maintain the therapeutic drug level for a longer period; however, more studies are needed in this field.

Oleuropein attenuates cognitive dysfunction and oxidative stress induced by some anesthetic drugs in the hippocampal area of rats.

The present study was designed to evaluate the antioxidant effects of oleuropein against oxidative stress in the hippocampal area of rats. We used seven experimental groups as follows: Control, Propofol, Propofol-Ketamine (Pro.-Ket.), Xylazine-Ketamine (Xyl.-Ket.), and three oleuropein-pretreated groups (Ole.-Pro., Ole.-Pro.-Ket. and Ole.-Xyl.-Ket.). The oleuropein-pretreated groups received oleuropein (15 mg/kg body weight as orally) for 10 consecutive days. Propofol 100 mg/kg, xylazine 3 mg/kg, and ketamine 75 mg/kg once as ip was used on the 11th day of treatment. Spatial memory impairment and antioxidant status of hippocampus were measured via Morris water maze, lipid peroxidation marker, and antioxidant enzyme activities. Spatial memory impairment and lipid peroxidation significantly increased in Xyl.-Ket.-treated rats in comparison to the control, propofol, Ole.-Pro. and Ole.-Pro.-Ket. groups. Oleuropein pretreatment significantly reversed spatial memory impairment and lipid peroxidation in the Ole.-Xyl.-Ket. group as compared to the Xyl.-Ket.-treated rats. There was no significant difference between the control and the propofol group in lipid peroxidation and spatial memory status. Superoxide dismutase and catalase activities both significantly decreased in Xyl.-Ket.-treated rats when compared to the control, propofol, Ole.-Pro., Ole.-Pro.-Ket., and Ole.-Xyl.-Ket. groups. In contrast, glutathione peroxidase activity in Xyl.-Ket.-treated rats significantly increased as compared to the control, propofol, Pro.-Ket., Ole.-Pro., and Ole.-Pro.-Ket. groups. We concluded that xylazine in combination with ketamine is an oxidative anesthetic drug and oleuropein pretreatment attenuates cognitive dysfunction and oxidative stress induced by anesthesia in the hippocampal area of rats. We also confirmed the antioxidant properties of propofol as a promising antioxidant anesthetic agent.