Intravenous disposition kinetics, oral and intramuscular bioavailability and urinary excretion of norfloxacin nicotinate in donkeys


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An aqueous solution of norfloxacin nicotinate (NFN) was administered to donkeys (Aquus astnus) intravenously (once at 10 mg/kg), intramuscularly and orally (both routes once at 10 and 20 mg/kg, and for 5 days at 20 mg/kg/day). Blood samples were collected at predetermined times after each treatment and urine was sampled after intravenous drug administration. Serum NFN concentrations were determined by microbiological assay. Intravenous injection of NFN over 45–60 s resulted in seizures, profuse sweating and tachycardia. The intravenous half‐life (t1/2β was 209 ± 36 min, the apparent volume of distribution (Vd(area)) was 3.34 ± 0.58 L/kg, the total body clearance (ClE) was 1.092 ± 0.123 ± 102mL/min/kg and the renal clearance (C1R) was 0.411 ± 0.057 ± 102mL/min/kg. Oral bioavailability was rather poor (9.6% and 6.4% for the 10 and 20 mg/kg doses respectively). Multiple oral treatments did not result in any clinical gastrointestinal disturbances. After intramuscular administration (20 mg/kg), serum NFN concentrations > 0.25 μg/mL (necessary to inhibit the majority of gram‐negative bacteria isolated from horses) were maintained for 12 h. The intramuscular bioavailability was 31.5% and 18.8% for the 10 and 20 mg/kg doses respectively. After multiple dosing some local swelling was observed at the injection site. About 40% of the intravenous dose was recovered in the urine as parent drug. The results of comprehensive haematological and blood biochemistry tests indicated no abnormal findings except elevation in serum CPK (creatine phosphokinase) values after multiple intramuscular dosing. On the basis of the in vitro‐determined minimum inhibitory concentrations of the drug and serum concentrations after multiple dosing, the suggested intramuscular dosage schedules for the treatment of gram‐negative bacterial infections in Equidae are 10 mg/kg every 12 h or 20 mg/kg every 24 h.

Original languageAmerican English
Pages (from-to)101-107
Number of pages7
JournalJournal of Veterinary Pharmacology and Therapeutics
Issue number2
StatePublished - Apr 1995


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