Fecal and urinary excretion of norfloxacin in adults
Motohiro, T.; Oda, K.; Aramaki, M.; Kawakami, A.; Tanaka, K.; Koga, T.; Shimada, Y.; Tomita, S.; Sakata, Y.; Fujimoto, T.
Japanese Journal of Antibiotics 40(11): 1869-1880
1987
ISSN/ISBN: 0368-2781 PMID: 3444027 Document Number: 291081
Norfloxacin (NFLX) a synthetic oral antibacterial agent of quinolone carboxylic acid, was given to 6 healthy men aged 23 to 29 years and weighing 57 to 88 kg (average 64.7 kg) at a dose of 200 mg (two 100 mg tablets) once after breakfast and its fecal and urinary recoveries were determined for 5 days after the administration. Fecal and urinary recoveries of NFLX or ciprofloxacin (CPFX) were examined under various experimental conditions where the drugs were added to the urine or feces. Effects of the drug on the clinical laboratory test parameters and side effects were also examined. The following results were obtained. 1. NFLX reached the highest level in the feces in 5 cases in 24 hours and in 1 case in 48 hours; average peak fecal level was 137.1 .mu.g/g in 24 hours. Fecal recoveries were 2.32 to 36.90% in 5 days after dosing with an average of 13.83%. 2. Urinary levels of the drug reached their peaks within 24 hours (average 51.46 .mu.g/ml) in all cases and then decreased. Urinary recoveries were 11.15 to 46.44% in 5 days after dosing. Both fecal and urinary levels of the drug varied greatly among the subjects. 3. The sum of the fecal and the urinary recoveries in each case varied from 13.47 to 76.88% (average 42.24%). 4. Since the sum of the fecal and the urinary recoveries was very low, the fecal recoveries were determined by adding NFLX to fecal samples at 0, 125, 500 and 2,000 .mu.g/g and concentrations were assayed. Recoveries were as low as 48.7 to 57.8%. Therefore, the potential influence of the 2 procedures (mixing and homogenation) on the drug recoveries was examined. No difference between 2 procedures existed. When another drug of a similar type, CPFX, was added to the feces, its recovery was aslo low. Then, the drug residual levels were 89.0, 86.0 and 78.2% immediately after the addition of the drug to GAM broth and after incubation for 6 and for 18 hours at 35.degree.C, respectively. Slightly reduced recoveries were obtained with longer time of incubation. Remaining drug levels in feces were determined following the addition of the drug at 50 .mu.g/ml in the presence of 1010 cells/ml of Bacteroides fragilis, a common strain of the fecal flora, in 1.0 ml of the GAM broth and recoveries with time were examined against 0-time recovery rate which was defined as 100. Recovery rates were reduced to 85.8 and 74.4% after incubation for 6 hours and for 18 hours at 35.degree.C, respectively. It is considered that B. fragilis might affect the NLFX level in te feces through an unknown mechanism. In addition, NFLUX recovery levels seem to change slightly dependent on the temperature. 5. From the 6 cases, 2 cases where the drug recoveries were determined following the addition of the drug were excluded, and feces were collected before the administration of NFLX in the remaining 4 cases, and the drug was added by mixing at concentrations of 200 and 800 .mu.g/g. Recoveries of the drug were 50.0 to 56.5% upon the addition of 200 .mu.g/g and 52.4 to 61.6% upon the addition of 800 .mu.g/g. This low recovery rates might be partly due to the interference with B. fragilis and partly due to temperature-dependency. 6. Abdominal pain and diarrhea occurred in 1 case following the administration of 200 mg. No abnormal result was noted in any case in clinical laboratory tests.