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Pharmacokinetics of danofloxacin in horses after intravenous, intramuscular and intragastric administration
Author(s) -
FERNÁNDEZVARÓN E.,
AYALA I.,
MARÍN P.,
CARRIÓN A.,
MARTOS N.,
ESCUDERO E.,
CÁRCELES C. M.
Publication year - 2006
Publication title -
equine veterinary journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.82
H-Index - 87
eISSN - 2042-3306
pISSN - 0425-1644
DOI - 10.2746/042516406777749245
Subject(s) - danofloxacin , pharmacokinetics , cmax , bioavailability , pharmacology , tolerability , oral administration , chemistry , medicine , dosing , adverse effect , antibiotics , norfloxacin , biochemistry , ciprofloxacin
Summary Reasons for performing study : Danofloxacin is a fluoroquinolone developed for veterinary medicine showing an excellent activity. However, danofloxacin pharmacokinetics profile have not been studied in horses previously. Objective : To study the pharmacokinetics following i.v., i.m. and intragastric (i.g.) administration of 1.25 mg/kg bwt danofloxacin to 6 healthy horses. Methods : A cross‐over design was used in 3 phases (2 times 2 × 2), with 2 washout periods of 15 days (n = 6). Danofloxacin (18%) was administered by i.v. and i.m. routes at single doses of 1.25 mg/kg bwt. For i.g. administration an oral solution was prepared and administered via nasogastric tube. Danofloxacin concentrations were determined by HPLC assay with fluorescence detection. Tolerability at the the site of i.m. injection was monitored by creatine kinase (CK) activity. Results : Danofloxacin plasma concentration vs. time data after i.v. and i.g. administration could best be described by a 2‐compartment open model. The disposition of i.m. administered danofloxacin was best described by a one‐compartment model. The terminal half‐lives for i.v., i.m. and i.g. routes were 6.31, 5.36 and 4.74 h, respectively. Clearance value after i.v. dosing was 0.34 l/kg bwt/h. After i.m. administration, absolute bioavailability was mean ± s.d. 88.48 ± 11.10% and C max was 0.35 ± 0.05 mg/l. After i.g. administration, absolute bioavailability was 22.36 ± 6.84% and C max 0.21 ± 0.07 mg/l. CK activity following i.m. dosing increased 3‐fold over pre‐injection levels 12 h after dosing and subsequently approached (but did not reach) normal values at 72 h post dose. Conclusions : Systemic danofloxacin exposure achieved in horses following i.m. administration was consistent with the predicted blood levels needed for a positive therapeutic outcome for many equine infections. Conversely, danofloxacin utility by the i.g. route was limited by low bioavailability. Tolerability associated with i.m. administration was high. Potential relevance : Pharmacokinetics, blood levels and good tolerability of i.v. and i.m. administration of danofloxacin in horses indicates that it is likely to be effective for treating sensitive bacterial infections.