Title of Thesis
Pharmacokinetics of Ciprofloxacin in Normal and
Different Metabolically Altered Conditions in Rabbits
University College of Pharmacy / University of
the Punjab, Lahore
|Number of Pages|
|Keywords (Extracted from title, table of contents and
abstract of thesis)|
Normal, Different, Metabolically, Altered, Conditions, alloxinized, Rabbits, flouroquinolone, hyperthermic
ciprofloxacin is a flouroquinolone antibacterial drug with outstanding activity against gram-negative and some gram positive bacteria. The pharmacokinetic parameters of ciprofloxacin following oral administration of a single dose of 20mg/Kg body weight were investigated in normal rabbits and in metabolically altered conditions. High performance liquid chromatographic method was employed for the determination of plasma concentrations of ciprofloxacin. The effect of these disease conditions on physiological/biochemical parameters like body weight and blood pH were also studied.
In water deprived rabbits, the mean plasma concentration AUC(0-t) and AUC
(0-∞) significantly were different as compared to normal rabbits. In physiological/biochemical parameters significant loss in body weight and an increase in packed cell volume, blood glucose and total lipids was observed. These results reflect a need for monitoring toxicity of ciprofloxacin in dehydrated rabbits.
There was no significant difference in body weight, blood pH, total protein and total lipids of febrile rabbits in comparison to the normal animals. However the value of packed cell volume, blood glucose, albumin and globulin were significantly lowered in febrile rabbits when compared to those of normal animals. In comparison to the normal rabbits significant increase in plasma drug concentration, absorption half life, distribution rate constant, elimination rate constant and AUC
(0-∞) was observed in febrile condition, where as a decrease in distribution half life and elimination half life was found in hyperthermic condition.
Body weight and packed cell volume were lowered and blood glucose, total protein, total lipids and globulin levels were significantly raised of diabetic animals when compared to normal rabbits. Plasma drug concentration, absorption half life, distribution rate constant, AUC
(0-t) and MRT were markedly decreased in alloxinized rabbits. Contrary absorption rate constant, elimination rate constant and C
max were increased under diabetic condition. The alloxan induced metabolic alteration was found to substantially influence pharmacokinetic parameters, which necessitates for an adjustment of the dose and dosage regimen of ciprofloxacin under such condition.
In the light of Changes observed in physiological biochemical and pharmacokinetic parameters of ciprofloxacin in metabolically altered conditions (dehydration, febrile and diabetic), it is suggested that such studies should be carried out in humans to make the safe effective and rational use of this valuable antibiotic.