Tissue distribution and binding to plasma proteins of norfloxacin nicotinate after intramuscular administration in pigs.

Three clinically normal pigs were given a single intramuscular injection of an aqueous solution of norfloxacin nicotinate (NFN) at 14 mg/kg body weight. Animals were killed 4 h after treatment and the concentrations of norfloxacin in various biological fluids and tissues were determined by chemical (high performance liquid chromatography, HPLC) and microbiological assay methods. Drug distribution throughout the body was presented as actual concentrations (micrograms/ml and ppm) in each sample and as the ratio of drug concentration in tissue to drug concentration in plasma. Highest concentrations were found in the urine, kidney, liver and bile. The drug was not detected in ocular fluid, brain tissue (by microbiological assay), fat (by HPLC) and skin (by HPLC). Tissue-to-plasma concentrations ratios were near to, or greater than, 1.0 (HPLC assay) for the kidney, liver, spleen, muscle, lung, adrenals, salivary glands, pleural and synovial fluid, and smaller than 1.0 for cerebrospinal fluid, brain tissue and lymph nodes. Agreement between the chemical and microbiological assay results was variable, depending on the type of tissue and biological fluid tested. Binding of norfloxacin to plasma proteins in pig is low (23%-29%). The distribution pattern of the drug in pig, laboratory animals and humans is very similar; it can be characterized as extensive, with tissue-to-serum ratios reaching 2:1 or more in certain non-excretory organs. These values may reflect intracellular concentrations of the drug.