Harshad B. Patel

Toxicopathological evaluation in Wistar rats (Rattus norvegicus) following repeated oral exposure to acephate

The present study was carried out to evaluate the effects of exposure at different doses of acephate on hematology, blood biochemistry, oxidative stress and immune system of Wistar rats. The experiment was carried out on 40 Wistar rats, which were divided in four groups. Animals of the three treatment groups were given with different sublethal doses (1/40th, 1/20th, 1/10th of lethal dose 50 value) of acephate by oral gavage. The hematology, blood biochemistry, oxidative stress marker, humoral immune response and cell-mediated immunity were evaluated following acephate exposure. Significant alteration in hematological parameters was not observed following different doses of acephate; however, significant alteration in alkaline phosphatase, gamma glutamyl transferase, acetyl cholinesterase, lipid peroxidase and superoxide dismutase was observed in medium- and high-dose group animals. Nonsignificant decrease in antibody titer in animals exposed to high dose has been observed compared with animals of control group. However, significant alteration in cell-mediated immunity was not observed in animals treated with acephate at different doses.

Disposition Kinetic of Moxifloxacin following Intravenous, Intramuscular, and Subcutaneous Administration in Goats.

The present study was carried out to investigate disposition kinetics of moxifloxacin following single-dose intravenous (i.v.), intramuscular (i.m.), and subcutaneous (s.c.) administration at a dose rate of 5 mg/kg of body weight (b.wt.) in goats. Plasma samples collected after treatments were analyzed for drug concentration using high-performance liquid chromatography (HPLC). After i.v. administration, distribution of the drug was rapid and wide as reflected by high steady-state volume of distribution. Drug elimination was relatively faster with a total body clearance of 0.59 ± 0.03 L/h/kg. Following i.m. injection, the drug has shown the rapid and near-to-complete absorption with bioavailability of 98.20 ± 3.96 per cent. The maximum plasma drug concentration (Cmax) of 1.21 ± 0.04 μg/mL was attained at 1 h (Tmax). The drug was widely distributed as reflected by high apparent volume of distribution. The elimination half-life (t 1/2β) of the drug was 6.26 ± 0.08  h. Following s.c. administration, the drug was rapidly absorbed (Cmax: 1.16 ± 0.02 μg/mL; tmax: 1 h) and slowly eliminated from the body. The elimination half-life and total body clearance (ClB) were 5.61 ± 0.10 h and 0.60 ± 0.03 L/h/kg, respectively. The bioavailability of moxifloxacin following s.c. administration was 90.44 ± 3.96 per cent.

Plasma Disposition of Conventional and Long-Acting Moxifloxacin in Sheep after Intravenous Administration

This study describes disposition of long-acting moxifloxacin and conventional formulations of moxifloxacin in sheep after intravenous administration in five male sheep. Long acting moxifloxacin solution (10% moxifloxacin in solution with L-arginine, N-butyl alcohol, and benzyl alcohol) and conventional moxifloxacin (10%) were injected in jugular vein. Blood samples were collected from contralateral jugular vein in test tubes containing 30–50 IU heparin (anticoagulant) periodically from 0.083 to 72 h of drug administration. Drug concentrations in plasma were determined using High-Performance Liquid Chromatography (HPLC) with fluorescence detector. The mobile phase consisted of a mixture of buffer (10 gm of tetrabutyl ammonium hydrogen sulphate per liter-deionised water) and acetonitrile (80 : 20). The buffer was 0.067M of disodium hydrogen phosphate with pH of 7.5. The flow rate was 1 mL·min−1 at ambient temperature. The effluent was monitored at 296 nm excitation and 504 nm emissions wavelength. HPLC with fluorescence detector method for plasma moxifloxacin assay was standardized with specific modification for plasma of sheep in the present study. After single-dose intravenous administration of long acting moxifloxacin the plasma concentration of 0.016 ± 0.001 μg·mL−1 was maintained for up to 72 h. Conventional formulation of moxifloxacin remained in body for up to 24 h of drug administration with the level of 0.015 ± 0.005 μg·mL−1.