Pharmacology
Seyed Ali Ayati Najafabadi; Ali Rassouli; Goudarz Sadeghi-Hashjin
Volume 15, Issue 2 , February 2024, , Pages 97-104
Abstract
Aminoglycoside antibiotics (AGs) can cause neuromuscular blockade and paralysis of skeletal muscles. To compare the paralytic effects of selected AGs on some motor behaviors in mice, 24 male mice weighing 20.00 to 25.00 g were divided into four treatment groups. Each group was given one of four AGs (gentamicin, ...
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Aminoglycoside antibiotics (AGs) can cause neuromuscular blockade and paralysis of skeletal muscles. To compare the paralytic effects of selected AGs on some motor behaviors in mice, 24 male mice weighing 20.00 to 25.00 g were divided into four treatment groups. Each group was given one of four AGs (gentamicin, dihydrostreptomycin, apramycin and amikacin) at incremental doses that increased half-logarithmically compared to the therapeutic dose (16.00 mg kg-1). Motor behavioral tests included open field test, inclined plane, horizontal bars, static rods, parallel bars and rotarod. Finally, the data were analyzed using descriptive and analytical statistics. Gentamicin and dihydrostreptomycin at 32.00 times of the therapeutic dose produced complete paralysis of the limbs, respiratory arrest, and even death in some animals. However, apramycin and amikacin did not show significant effects on skeletal muscle and motor behaviors at 32.00 times of the therapeutic dose. After administration of apramycin at 100 times of the therapeutic dose, four out of six mice (66.67%) died from respiratory depression. Amikacin at this dose did not cause animal death, although it caused some changes in motor behaviors with a significant difference in comparison with control values. Gentamicin demonstrated significantly more potent effects on motor behaviors compared to the other AGs. Overall, the order of potency was gentamicin > dihydrostreptomycin > apramycin > amikacin. High doses of AGs could impair the skeletal muscle function and disrupt motor behaviors in mice. Furthermore, the paralytic potency of selected AGs on skeletal muscle was significantly different.
Ali Rassouli; Katayoun Kiani; Yalda Hosseizadeh Ardakani; Hamid Akbari Javar; Sakineh Khanamani Falahatipour
Volume 12, Issue 2 , June 2021, , Pages 253-257
Abstract
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. ...
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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 β-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 concentrationversustime 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 perhr) 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.
