Pharmacokinetics of danofloxacin in horses after intravenous, intramuscular and intragastric administration.
BACKGROUND
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 x 2 x 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 Cmax was 0.35 +/- 0.05 mg/l. After i.g. administration, absolute bioavailability was 22.36 +/- 6.84% and Cmax 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.


CONCLUSIONS
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.
Fernández-Varón
E
E
Department of Pharmacology, Faculty of Veterinary Medicine, University of Murcia, Spain.
Ayala
I
I
Marín
P
P
Carrión
A
A
Martos
N
N
Escudero
E
E
Cárceles
C M
CM
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001424:Bacterial Infections / Q000188:drug therapy / Q000662:veterinary*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000662:veterinary; D003402:Creatine Kinase / Q000378:metabolism; D018592:Cross-Over Studies; D005453:Fluorescence; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D007441:Intubation, Gastrointestinal / Q000662:veterinary
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C068581:danofloxacin; D003402:Creatine Kinase