Pharmacokinetics and tissue residues of norfloxacin and its N‐desethyl‐ and oxo‐metabolites in healthy pigs

Abstract

The pharmacokinetic properties of norfloxacin were determined in healthy pigs after single intramuscular (i.m.) and intravenous (i.v.) dosage of 8 mg/kg body weight. After i.m. and i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. After single i.m. administration, norfloxacin was absorbed rapidly, with a tmax of 1.46 +/- 0.06 h. The elimination half-life (t1/2 beta) and the mean residence time of norfloxacin in plasma were 4.99 +/- 0.28 and 6.05 +/- 0.22 h, respectively, after i.m. administration and 3.65 +/- 0.16 and 3.34 +/- 0.16 h, respectively, after i.v. administration. Intramuscular bioavailability was found to be 53.7 +/- 4.4%. Plasma concentrations greater than 0.2 microgram/mL were achieved at 20 min and persisted up to 8 h post-administration. Maximal plasma concentration was 1.11 +/- 0.03 micrograms/mL. Statistically significant differences between the two routes of administration were found for the half-lives of both distribution and elimination phases (t1/2 alpha, t1/2 beta) and apparent volume of distribution (Vd(area)). In pigs, norfloxacin was mainly converted to desethylenenorfloxacin and oxonorfloxacin. Considerable tissue concentrations of norfloxacin, desethylenenorfloxacin, and oxonorfloxacin were found when norfloxacin was administered intramuscularly (8 mg/kg on 4 consecutive days). The concentration of the parent fluoroquinolone in liver and kidney ranged between 0.015 and 0.017 microgram/g on day 12 after the end of dosing.

Susceptibility Breakpoint for Enrofloxacin against Swine Salmonella spp

“…Our results were in agreement with previous studies which indicated that ciprofloxacin levels (an active metabolite of enrofloxacin) were too low in the plasma of pigs and enrofloxacin could be served as the marker for PK calculation (10,11). Based on the concentration-time curve of plasma enrofloxacin, a series of pharmacokinetic parameters for the 12 piglets were derived from a one-compartment model (see Table 1).…”

Modification of Norfloxacin by a Microbacterium sp. Strain Isolated from a Wastewater Treatment Plant

“…strain 4N2-2. NH 4 ϩ and NO 2 Ϫ at this concentration did not enhance the production of hydroxylated metabolites, but NO 3 Ϫ enhanced it even without ascorbic acid. The production of 8-hydroxynorfloxacin and 6-defluoro-6-dehydroxynorfloxacin in 14-day cultures in OM medium with 1.0 g liter Ϫ1 NaNO 3 was 78% and 56%, respectively, of the production in regular OM medium with 0.5 mM ascorbic acid (data not shown).…”

“…The principal medium used, referred to as OM medium, was composed (per liter) of 1.0 g glucose, 50 mg NH 4 Enrichment cultures and strain isolation. Enrichment cultures (40 ml) in 250-ml flasks with 100 g ml Ϫ1 N-phenylpiperazine as the sole carbon source or nitrogen source were inoculated with aerobic liquor from a wastewater treatment plant in Little Rock, AR (28).…”

“…The product-ion spectrum (Table 1) showed a neutral loss of H 2 O from the carboxyl group (m/z 276), a subsequent HF loss indicating the presence of fluorine (m/z 256), and losses of C 2 H 5 N (m/z 233) and NH 3 (m/z 277) from the remainder of the piperazine ring. Loss of NH 3 is evidence of piperazine desethylation.…”

“…Production of the hydroxylated metabolites was almost abolished by formate and thiourea, but mannitol allowed production of ca. 13% and 38% of the hydroxylated metabolites in media with ascorbic acid and NO 3 Ϫ , respectively (Fig. 4).…”