Effect of Norfloxacin on Human Oropharyngeal and Colonic Microflora and Multiple-dose Pharmacokinetics

Abstract

10 healthy volunteers received 200 mg norfloxacin orally every 12 h for 7 days. Saliva, throat and faecal specimens were collected days 0, 3, 5, 7, 14 and 21 to study the effect of norfloxacin on the normal microflora. The concentrations of norfloxacin in serum, urine, saliva and faeces were determined by a microbiological method and all samples except faeces were also assayed by high-pressure liquid chromatography (HPLC). The pharmacokinetics of norfloxacin were studied on day 3. The mean peak serum concentration (+/- SD) attained after 0.75-1.0 h was 0.75 +/- 0.15 mg/l measured by HPLC, and the mean terminal serum half-life was 4.2 +/- 0.6 h. The mean cumulative urinary elimination was 29% during 12 h after dosing. There was no significant difference between values obtained by microbiological assay and by HPLC. The saliva concentration was approximately 30% of the serum levels 1.0-1.5 h after administration. No accumulation in faeces was found during the administration period, and mean concentrations were 940 mg/kg. The changes in the oropharyngeal flora were minor and only branhamella were affected. In the colonic flora, the number of enterobacteria was strongly depressed while the anaerobic microflora was only slightly affected. Two weeks after the administration period, both the oropharyngeal and colonic microflora had returned to normal.

A norfloxacin dose finding study for selective decontamination of the digestive tract in pigs

“…De Vries-Hospers, Welling & van der Waaij (1985) found that, in ten human volunteers, daily oral treatment with 200 mg, 400 mg or 800 mg norfloxacin resulted in Enterobacteriaceae-free stool cultures after 3-5 days. A similar period of norfloxacin treatment was required for negative stool cultures in another study by Pecquet and co-authors (1985) as well as by Edlund et al (1987). In our pigs, it also took 5 or 3 days of treatment with the dosages used (400 mg/day and 800 mg/day respectively) before their stools were negative.…”

“…In the studies of human subjects by De Vries-Hospers, Welling & van der Waaij (1985), the average faecal norfloxacin concentration during treatment with 200 mg, 400 mg and 800 mg per day was higher than we found in the pig. Also Gilfillan, Pelak & Bland (1984) as well as Edlund et al (1987) also reported relatively high average concentrations of 700-1000 mg/kg of faeces at the third day of treatment with 400 mg per day. Pecquet and co-authors (1985), also studying human volunteers, reported even higher concentrations between 1000 and 5000 mg/kg of faeces with a mean of 2500 mg/kg during treatment with 200 mg norfloxacin per day and 4000 mg/kg faeces during daily administration of 400 mg.…”

“…However, the DMCC and the concentration of enterococci were not changed. The fact that the DMCC was not changed during norfloxacin treatment, regardless the fact that (perhaps inactive) concentrations existed in the faeces far in excess of the MIC's of most if not all anaerobic intestinal bacteria, could be explained if, as described by Edlund et al (1987), faecal substance complexes strongly with norfloxacin. After suspending faeces with (bio-inactive) norfloxacin, part of the complexed norfloxacin may be dissociated and return to activity.…”

“…In addition, norfloxacin has recently been found very effective and safe for SD in man (Pecquet, Andremont & Tancrede, 1985;Winston et al 1987;Edlund et al 1987). However, regardless of its apparent safety, there remains a question concerning the maintenance of the indigenous intestinal flora.…”

Comparative Pharmacokinetic Profiles of Two Norfloxacin Formulations after Oral Administration in Rabbits.

“…After i.v. injection of NFLX, the elimination halflife (T 1/2β ) of 3.37 ± 1.37 hr in this study was similar to half-lives reported for mice, rats, dogs and monkeys [5], but shorter than the half-lives reported for horses [7], calves [13] and human beings [2]. The systemic clearance (Cl B ) of NFLX was 0.68 ± 0.18 l/kg/hr and the volume of distribution of NFLX at steady state (VD ss ) was 2.21 ± 1.07 L/kg.…”