Pharmacokinetic and toxicity studies of ofloxacin in poultry
Abstract
Ofloxacin, a new second generation fluorinated quinolone, possesses broad antimicrobial spectrum against gram-positive and gram-negative pathogens including obligate anaerobes. These excellent antimicrobial characteristics of ofloxacin indicate its high potential in treating common infections such as mycoplasmosis, colibacillosis, pasteurollosis etc. in chicken. For successful therapeutic application, the pharmacokinetic and toxicity studies of ofloxacin were conducted in adult female WLH chicken
Ofloxacin concentrations in plasma were determined using a high performance liquid chromatography (HPLC) assay. Various pharmacokinetic parameters were computed by using a non linear iterative curve fitting computer program ‘PHARMKIT’. The disposition of ofloxacin followed two-compartment open model following single i.v. administration (10 mg.kg-1b.wt.) with rapid distribution. The distribution rate constant (), elimination rate constant (), distribution half-life (t1/2) and elimination half-life (t½) values were 8.21 h-1, 0.34 h-1, 0.09 h and 2.09 h, respectively. The values of k12, k21, kel and ClB were found to be 3.35 h-1, 4.16 h-1, 0.61 h-1 and 0.18 L.kg-1.h-1, respectively. The values of AUC, MRT, Vz(area) and tcp(ther) were 63.61 g.ml-1.h, 2.93 h, 0.51 L.kg-1 and 14.09 h, respectively.
The disposition kinetics of ofloxacin was adequately described by one-compartment open model after absorption phase following single
oral administration (10 mg.kg-1). Ofloxacin was rapidly absorbed and the maximum concentration of Ofloxacin was observed to be 3.40 g.ml-1 1 h t(max). The values of ka, t½ka, and t½ were determined to be 2.69 h-1, 0.27 h, 0.29 h-1 and 2.47 h, respectively. The calculated values of Vz(area), Cl, MRT and tcp(ther) were 0.89 L.kg-1, 0.25 L.kg-1.h-1, 4.43 h and 14.68 h, respectively.
Considering MIC as 0.5 g.ml-1, the loading and maintenance doses of ofloxacin were computed to be 1.95 and 0.70 mg.kg-1, respectively at a dosage interval of 6 hours following i.v. route. The values of loading and maintenance doses of ofloxacin following oral administration were determined to be 2.45 and 0.90 mg.kg-1 at the same dosage interval of 6 h in adult WLH chicken.
In acute toxicity study, no significant effect was observed on various haematological parameters viz. Hb, PCV, TEC at 6, 24 and 72 h following single oral administration of ofloxacin at a dose rate of 20 mg.kg-1 b.wt. in adult WLH chicken. Ofloxacin caused significant decrease in total protein and albumin, but significant increase in the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at 24 h. There was no significant effect on creatinine. Mild histopathological lesions were also observed in liver and kidney at 24 h. However, this effect was found to be reversible and all biochemical and histopathological changes became normal at 72 h.
In subacute toxicity study, ofloxacin did not cause any significant effect on haematological parameters viz. Hb, PCV, TEC on 7, 14 and 21days following daily oral administration at a dose of 10 mg.kg-1 b. wt for 14 days. Ofloxacin caused significant decrease in total protein and albumin content. A significant increase in the levels of AST and ALT was observed on 14th day. Ofloxacin did not cause any significant effect on creatinine. Mild to moderate histopathological lesions were observed in liver and kidney on 14th day. However, all the biochemical and histopathological changes became normal on 21st day in adult female WLH chicken.