INTRAVENOUS DISPOSITION KINETICS, ORAL AND INTRAMUSCULAR BIOAVAILABILITY AND URINARY-EXCRETION OF NORFLOXACIN NICOTINATE IN DONKEYS

An aqueous solution of norfloxacin nicotinate (NFN) was administered t o donkeys (Aquus asinus) intravenously (once at 10 mg/kg), intramuscul arly and orally (both routes once at 10 and 20 mg/kg, and for 5 days a t 20 mg/kg/day). Blood samples were collected at predetermined times a fter each treatment and urine was sampled after intravenous drug admin istration. Serum NFN concentrations were determined by microbiological assay. Intravenous injection of NPN over 45-60 s resulted in seizures , profuse sweating and tachycardia. The intravenous half-life (t(1/2 b eta)) was 209 +/- 36 min, the apparent volume of distribution (V-d(are a) was 3.34 +/- 0.58 L/kg, the total body clearance (C1(R)) was 1.092 +/- 0.123 x 10(-2) mL/min/kg and the renal clearance (C1(R)) was 0.411 +/- 0.057 x 10(-2) mL/min/kg. Oral bioavailability was rather poor (9 .6% and 6.4% for the 10 and 20 mg/kg doses respectively). Multiple ora l treatments did not result in any clinical gastrointestinal disturban ces. After intramuscular administration (20 mg/kg), serum NFN concentr ations > 0.25 mu g/mL (necessary to inhibit the majority of gram-negat ive bacteria isolated from horses) were maintained for 12 h. The intra muscular bioavailability was 31.5% and 18.8% for the 10 and 20 mg/kg d oses respectively. After multiple dosing some local swelling was obser ved at the injection site. About 40% of the intravenous dose was recov ered in the urine as parent drug. The results of comprehensive haemato logical and blood biochemistry tests indicated no abnormal findings ex cept elevation in serum CPK (creatine phosphokinase) values after mult iple intramuscular dosing. On the basis of the in vitro-determined min imum inhibitory concentrations of the drug and serum concentrations af ter multiple dosing, the suggested intramuscular dosage schedules for the treatment of gramnegative bacterial infections in Equidae are 10 m g/kg every 12 h or 20 mg/kg every 24 h.