A Comprehensive Model for Enrofloxacin to Ciprofloxacin Transformation and Disposition in Dog

Abstract

The pharmacokinetics of enrofloxacin and ciprofloxacin, its major active metabolite, were determined in dog after oral and intravenous administrations of enrofloxacin and intravenous infusion of ciprofloxacin. A comprehensive model of enrofloxacin and ciprofloxacin disposition was constructed to investigate the extent of enrofloxacin to ciprofloxacin transformation and the influence of the hepatic first-pass effect on the parent compound oral bioavailability. Plasma levels were measured using a validated HPLC method. Enrofloxacin and ciprofloxacin plasma concentration data were fitted simultaneously using a set of differential equations describing a six-compartment model (two compartments for each analyte, one for the liver, and one for the intestinal tract); it was assumed that only a fraction of enrofloxacin was metabolized to ciprofloxacin and that this conversion only occurred in the liver. The fitted parameters obtained from the model were used to calculate plasma clearances (0.729 +/- 0.212 L/h/kg for enrofloxacin, 0.468 +/- 0.094 L/h/kg for ciprofloxacin), distribution volumes (2.45 +/- 0.49 L/kg for enrofloxacin, 1.92 +/- 0.33 L/kg for ciprofloxacin), mean residence times (3.47 +/- 0.78 h for enrofloxacin, 4.20 +/- 0.82 h for ciprofloxacin), and the fractions of enrofloxacin metabolized to ciprofloxacin after intravenous and oral administrations of enrofloxacin. It was shown that enrofloxacin was largely metabolized to ciprofloxacin and that the fractions of metabolized enrofloxacin were similar after intravenous and oral administrations of enrofloxacin (40.44 +/- 10.08 and 40.17 +/- 8.33%, respectively), the hepatic first-pass effect being low (7.15 +/- 1.99%).

Activity–Bioavailability balance in Oral Drug Development for a Selected Group of 6‐Fluoroquinolones

“…The 4′ N ‐alkylciprofloxacin derivatives were selected for this study. As perfect homologs, they tend to generate ciprofloxacin as a metabolite in variable proportion in the long run; despite this, however, they should not be regarded merely as ciprofloxacin prodrugs, as has sometimes been postulated 20,21. On the contrary, as will be seen later, they greatly differ from ciprofloxacin in terms of both activity and bioavailability.…”

“…A good criterion for predicting the absolute oral bioavailability of any compound belonging to any series is to use its in situ absorption rate constant, k a , determined in the rat small intestine. As pointed out recently,1 when substantial presystemic losses are not expected, as occurs with quinolones,4,6,21 a mathematical expression that predicts their absolute oral bioavailability is as follows: …”

Computational simulation and preparation of fluorescent magnetic molecularly imprinted silica nanospheres for ciprofloxacin or norfloxacin sensing

“…Therefore, monitoring FQs residues in biological samples and animal products is of great importance. Several methods for determining the residues of FQs have been developed in recent years, such as spectrophotometry , CE , and LC methods . Most of these methods involve two steps including a preliminary extraction and a second clean‐up step with LLE or SPE.…”

An ionizable chromophoric reagent for the analysis of primary amine-containing drugs by capillary electrophoresis

“…OAC was derived from ofloxacin, a fluoroquinolone antibacterial. Fluoroquinolones have good chromophore or fluorophore characteristics and are frequently analyzed by ultraviolet spectrometry (UV) or fluorimetry [4][5][6][7][8][9][10][11]. Figure 1 shows that OAC has an acyl function for labeling and making amino analytes chromophoric.…”