Pharmacokinetics of ibafloxacin in healthy cats

Abstract

The pharmacokinetics of ibafloxacin following single and repeated administration of an oral gel formulation and the effect of food intake were investigated in cats. Ibafloxacin is a chiral fluoroquinolone available for clinical use as a racemic mixture of the R- and S-enantiomers. Plasma concentrations of ibafloxacin and its metabolites were determined using microbiological, LC-MS-MS and enantioselective capillary zone electrophoresis assays. Ibafloxacin was absorbed rapidly [time of maximum concentration (tmax) 2-3 h], reaching a mean maximum concentration (Cmax) of approximately 2.1 and 1.6 microg/mL for R- and S-ibafloxacin, respectively, following a single oral administration of the racemate at 15 mg/kg. Once absorbed, ibafloxacin was metabolized to 7-hydroxy-ibafloxacin and mainly to 8-hydroxy-ibafloxacin. Following repeated oral administration, significant increases in Cmax and AUC of ibafloxacin and its less active metabolites (racemic or enantiomers) were observed between the first and the tenth day of treatment. This twofold exposure increase in concentrations of ibafloxacin and its metabolites may contribute additionally to the efficacy of this drug in the treatment of feline bacterial infections. Single and repeated doses of ibafloxacin were well tolerated by cats. Food promoted the absorption of ibafloxacin, doubling Cmax and increasing AUC and slightly delaying tmax. High concentrations of the metabolites, mainly 8-hydroxy- and 7-hydroxy-ibafloxacin were excreted in urine, either unchanged or as glucurono-conjugates.

Stereoselective determination of drugs and metabolites in body fluids, tissues and microsomal preparations by capillary electrophoresis (2000–2010)

“…Other investigations dealt with the complete elucidation of the pharmacokinetics via analysis of the drug enantiomers in plasma or serum. Examples studied included the drugs anisodamine [75], carvedilol [78], ibafloxacine [81], ibuprofen [82,83], indobufen [84], ketoprofen [85], trans-tramadol [91,93], venlafaxine [94] and ketamine [157,160,161,163]. For one drug, carvedilol, enantiomer plasma concentrations were found to be comparable to those determined by HPLC [78].…”

Pharmacodynamics of ibafloxacin in micro‐organisms isolated from cats

“…By using the in vivo pharmacokinetic parameters from LC–MS–MS (arithmetic mean on days 1, 5 and 10 of treatment; Coulet et al. , 2004) and the in vitro MIC 90 data, surrogate markers of antimicrobial activity, C max / MIC 90 , AUC / MIC 90 and t > MIC 90 , the time during which plasma racemic ibafloxacin concentrations exceeded 0.5 μ g/mL, were determined.…”

“…The pharmacokinetic parameters were estimated from LC–MS–MS and CZE results on days 1, 5 and 10 in a pharmacokinetic study in cats that were treated with 15 mg racemic ibafloxacin/kg once daily for 10 consecutive days (Coulet et al. , 2004).…”

“…By using the in vivo pharmacokinetic parameters from LC-MS-MS (arithmetic mean on days 1, 5 and 10 of treatment; Coulet et al, 2004) and the in vitro MIC 90 data, surrogate markers of antimicrobial activity, C max /MIC 90 , AUC/MIC 90 and t > MIC 90 , the time during which plasma racemic ibafloxacin concentrations exceeded 0.5 lg/mL, were determined. In addition, by using the in vivo pharmacokinetic parameters from capillary zone electrophoresis (CZE) (arithmetic mean on days 1, 5 and 10 of treatment; Coulet et al, 2004) and in vitro MIC data, C max / MIC, AUC/MIC and t > MIC, the time during which plasma S-ibafloxacin concentrations exceeded MIC were estimated.…”

“…The pharmacokinetic parameters were estimated from LC-MS-MS and CZE results on days 1, 5 and 10 in a pharmacokinetic study in cats that were treated with 15 mg racemic ibafloxacin/ kg once daily for 10 consecutive days (Coulet et al, 2004). The MIC of 0.5 lg/mL, a concentration that incorporates the MIC 90 for the majority of micro-organisms that are considered susceptible to racemic ibafloxacin, was used to calculate the C max /MIC 90 ratio, AUC/MIC 90 ratio and t > MIC 90 (Table 3).…”