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

The research investigates how an aqueous solution of Norfloxacin Nicotinate (NFN) is metabolised and excreted when administered to donkeys intravenously, orally and intramuscularly at various doses. The findings reveal that NFN’s oral bioavailability is poor, and while intramuscular doses are somewhat more effective, they may cause local swelling at the injection site.

Study Design and Process

• The study involves administering an aqueous solution of Norfloxacin Nicotinate (NFN), a type of antibiotic, to donkeys via three different routes – intravenously (once at 10 mg/kg), intramusically, 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 various predetermined times following each treatment, and urine was collected after the intravenous administration of the drug.
• The concentration of NFN in the serum was determined using a microbiological assay, a test that measures the effect of the substance on bacteria.

Findings and Observations

• When NFN was administered intravenously, it resulted in seizures, profuse sweating, and rapid heartbeats in the animals. Additionally, about 40% of the intravenous dose was found in the urine as the parent drug meaning the drug was not metabolized before it was excreted.
• The study shows that the half-life – the time it takes for the amount of drug in the body to reduce by half – was approximately 209 minutes. The apparent volume of distribution, which is a measure of the extent of a drug’s distribution in the body tissues, was 3.34 litres per kg. The total body clearance, measuring how quickly the drug is cleared from the body, was 1.092 x 10(-2) mL/min/kg while the renal clearance (assessing the kidney’s efficiency in removing drug from the blood and excreting it into urine) was 0.411 x 10(-2) mL/min/kg.
• NFN’s oral bioavailability, which is the degree to which a drug is available to the body for use, was found to be poor at 9.6% and 6.4% for the 10 and 20 mg/kg doses respectively. Multiple oral administrations did not lead to any clinical gastrointestinal disturbances.
• In the case of intramuscular administration, serum concentrations of NFN remained high enough to inhibit most Gram-negative bacteria (a typology of bacteria) for 12 hours. The bioavailability was 31.5% and 18.8% for the 10 and 20 mg/kg doses respectively. However, some swelling was observed at the injection sites after multiple dosings.
• The study didn’t highlight any significant abnormal findings from comprehensive haematological and blood biochemistry tests, except for an elevated level of serum CPK (an enzyme called creatine phosphokinase) following multiple intramuscular doses.