PHARMACOKINETICS, HEMATOLOGICAL AND BIOCHEMICAL EFFECTS OF CIPROFLOXACIN HYDROCHLORIDE-SODIUM CHOLATE COMPLEX

Objective: Ciprofloxacin is a broad spectrum antibiotic widely used in the treatment of infections, but its toxicological effects remains a great challenge. This research emphasized on analyzing the effect of a hydrophobic ion pair complex, involving ciprofloxacin hydrochloride and sodium cholate and also pegylated ciprofloxacin hydrochloride-sodium cholate complex . Methods: The effects of ciprofloxacin-cholate complex and pegylated ciprofloxacin-cholate complex were evaluated . LD 50 was determined. The test drugs were orally to twenty-four albino mice, in six groups of four mice, at different doses of 7.14 mg/kg, 14.2 mg/kg and 21.4 mg/kg; and PEG complex, 7.14 and 14.2 mg/kg. Each was administered twice daily for fourteen days. The animal blood samples were subjected to hematological, biochemical tests; and the liver organs were collected. Histopathological examination was carried out on the harvested organs. Pharmacokinetic parameters were determined using the non-compartmental method. Results: The LD 50 of the complex was above 5000 mg/kg. The non-significant decrease in PCV and WBC showed the parent drug and its complex are neither anemia inducing nor immunosuppressing; the significant decrease in the average RBCs count in post–treatment of 21.47 mg/kg of the complex could be from physiological changes; the bio-liver makers showed hepatocellular damage. Photomicrograph of the liver sections of mice showed mild areas of hepatocyte degeneration and inflammatory cell infiltrates. Conclusion: The biochemical, hematological and histology results showed complexation did not increase adverse effects of ciprofloxacin. The PEGYlated complex showed higher AUC and C max peak than the uncomplexed drug, hence more therapeutic benefits.