Pharmacokinetic properties and oral bioavailabilities of difloxacin in pig and chicken

Inui, Tomohiro; Taira, Tomoe; Matsushita, Takeji; Endo, Takuro

doi:10.1080/004982598239128

Cited by 21 publications

(17 citation statements)

References 8 publications

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“…These values are close to those reported in pigs and horses for difloxacin with an elimination half‐life after i.m. dosing of 7.92 (Inui et al. , 1998) and 5.72 h (Fernández‐Varón et al.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and milk penetration of difloxacin after intravenous, subcutaneous and intramuscular administration to lactating goats

Marı́n

Escudero

Fernández-Varón

et al. 2007

Vet Pharm & Therapeutics

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The single-dose disposition kinetics of difloxacin were determined in clinically normal lactating goats (n = 6) after intravenous (i.v.), subcutaneous (s.c.) and intramuscular (i.m.) administration of 5 mg/kg. Difloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. The concentration-time data were analysed by compartmental and noncompartmental kinetic methods. Steady-state volume of distribution (V(ss)) and total body clearance (Cl) of difloxacin after i.v. administration were estimated to be 1.16 +/- 0.26 L/kg and 0.32 +/- 0.05 L/h x kg respectively. Following s.c. and i.m. administration difloxacin achieved maximum plasma concentrations of 1.33 +/- 0.25 and 1.97 +/- 0.40 mg/L at 3.37 +/- 0.36 and 1.79 +/- 1.14 h respectively. The absolute bioavailabilities after s.c. and i.m. routes were 90.16 +/- 11.99% and 106.79 +/- 13.95% respectively. Difloxacin penetration from the blood into the milk was extensive and rapid, and the drug was detected for 36 h after i.v. and s.c. dosing, and for 72 h after i.m. administration.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and milk penetration of difloxacin after intravenous, subcutaneous and intramuscular administration to lactating goats

Marı́n

Escudero

Fernández-Varón

et al. 2007

Vet Pharm & Therapeutics

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“…Single daily doses of the three FQs for 3 consecutive days with simulated half-lives (t 1/2 ) consistent with those reported in pigs were used: 12.5 h for DIF (33,34), 10.6 h for ENR (35,36) and 8 h for MAR (37). The doses were selected to include the achievable area under the curve (AUC) and maximum plasma concentration (C max ) over a 24-h dosing interval at the recommended clinical doses (1 to 5 mg/kg of body weight for DIF, 2.5 to 5 mg/kg for ENR, and 2 mg/kg for MAR) in pigs.…”

Section: Methodsmentioning

confidence: 99%

Using In Vitro Dynamic Models To Evaluate Fluoroquinolone Activity against Emergence of Resistant Salmonella enterica Serovar Typhimurium

Lee

Awji²,

Park

et al. 2017

Antimicrob Agents Chemother

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The objectives of this study were to determine pharmacokinetic/pharmacodynamic (PK/PD) indices of fluoroquinolones that minimize the emergence of resistant Salmonella enterica serovar Typhimurium (S. Typhimurium) using in vitro dynamic models and to establish mechanisms of resistance. Three fluoroquinolones, difloxacin (DIF), enrofloxacin (ENR), and marbofloxacin (MAR), at five dose levels and 3 days of treatment were simulated. Bacterial killing-regrowth kinetics and emergence of resistant bacteria after antibacterial drug exposure were quantified. PK/PD indices associated with different levels of antibacterial activity were computed. Mechanisms of fluoroquinolone resistance were determined by analyzing target mutations in the quinolone resistance-determining regions (QRDRs) and by analyzing overexpression of efflux pumps. Maximum losses in susceptibility of fluoroquinoloneexposed S. Typhimurium occurred at a simulated AUC/MIC ratio (area under the concentration-time curve over 24 h in the steady state divided by the MIC) of 47 to 71. Target mutations in gyrA (S83F) and overexpression of acrAB-tolC contributed to decreased susceptibility in fluoroquinolone-exposed S. Typhimurium. The current data suggest AUC/MIC (AUC/mutant prevention concentration [MPC])-dependent selection of resistant mutants of S. Typhimurium, with AUC/MPC ratios of 69 (DIF), 62 (ENR), and 39 (MAR) being protective against selection of resistant mutants. These values could not be achieved in veterinary clinical areas under the current recommended therapeutic doses of the fluoroquinolones, suggesting the need to reassess the current dosing regimen to include both clinical efficacy and minimization of emergence of resistant bacteria.

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“…and or Mycoplasma spp. Although the pharmacokinetics of difloxacin has been investigated in a number of species, including chickens, pigs, dogs and goats (Inui et al, 1998;Frazier et al, 2000;Atef et al, 2002;Heinen, 2002;Abd El Aty et al, 2005), there are no reports evaluating the pharmacokinetics of the drug in calves.…”

Section: Introductionmentioning

confidence: 96%

“…Difloxacin is rapidly absorbed and has high systemic bioavailabilities following oral administration in chickens, pigs (Inui et al, 1998) and dogs (Frazier et al, 2000) as well as i.m. administration in rabbits (Abd el Aty et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Disposition Kinetics of Difloxacin After Intravenous, Intramuscular and Subcutaneous Administration in Calves

Ismail

2006

Vet Res Commun

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The pharmacokinetics of difloxacin (Dicural) was studied in a crossover study using three groups (n = 4) of male and female Friesian calves after intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administrations of 5 mg/kg body weight. Drug concentration in plasma was determined by high-performance liquid chromatography using fluorescence detection. The plasma concentration-time data following i.v. administration were best fitted to a two-compartment open model and those following i.m. and s.c. routes were best fitted using one-compartment open model. The collected data were subjected to a computerized kinetic analysis. The mean i.v., i.m. and s.c. elimination half-lives (t(1/2beta)) were 5.56 +/- 0.33 h, 6.12 +/- 0.42 h and 7.26 +/- 0.6 h, respectively. The steady-state volume of distribution (V(dss)) was 1.12 +/- 0.09 L/kg and total body clearance (Cl(B)) was 2.19 +/- 0.1 ml/(min x kg). The absorption half lives (t(1/2ab)) were 0.38 +/- 0.027 h and 2.1 +/- 0.09 h, with systemic bioavailabilities (F) of 96.5% +/- 6.4% and 84% +/- 5.5% after i.m. and s.c. administration, respectively. After i.m. and s.c. dosing, peak plasma concentrations (C(max)) of 3.38 +/- 0.13 microg/ml and 2.18 +/- 0.12 microg/ml were attained after (t(max)) 1.22 +/- 0.20 h and 3.7 +/- 0.52 h. The MIC90 of difloxacin for Mannheimia haemolytica was 0.29 +/- 0.04 microg/ml. The AUC/MIC90 and C(max)/MIC90 ratios for difloxacin following i.m. administration were 120 and 11.65, respectively and following s.c. administration were 97.58 and 7.51, respectively. Difloxacin was 31.7-36.8% bound to calf plasma protein. Since fluoroquinolones display concentration-dependent activities, the doses of difloxacin used in this study are likely to involve better pharmacodynamic characteristics that are associated with greater clinical efficacy following i.m. administration than following s.c. administration.

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Pharmacokinetic properties and oral bioavailabilities of difloxacin in pig and chicken

Cited by 21 publications

References 8 publications

Pharmacokinetics and milk penetration of difloxacin after intravenous, subcutaneous and intramuscular administration to lactating goats

Pharmacokinetics and milk penetration of difloxacin after intravenous, subcutaneous and intramuscular administration to lactating goats

Using In Vitro Dynamic Models To Evaluate Fluoroquinolone Activity against Emergence of Resistant Salmonella enterica Serovar Typhimurium

Disposition Kinetics of Difloxacin After Intravenous, Intramuscular and Subcutaneous Administration in Calves

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