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

Abstract

fluids were analyzed by high pressure liquid chromatography (HPLC) as reported previously [9].For the tissue distribution study, two rabbits were used as controls and six of twelve male rabbits were given by NFLXN with 5 mg equivalent NFLX/kg of body weight. The remaining six rabbits were administered NFLXGA with 5 mg equivalent NFLX/kg of body weight. After oral administration of NFLXN and NFLXGA, the rabbits were slaughtered at 2 hr and liver, kidney, lung, muscle and serum were collected from each animal. The collected organs were labeled and immediately frozen at 70°C until analysis by HPLC. The analytical curve for NFLX was linear from 0.05 to 10 mg/kg or l (R 2 =0.999). The precisions were as follows: plasma, 3%, kidney, 4.7%; liver, 7%; muscle tissue 8%. The limit of detection was 10 ng/ml in plasma and 30 ng/g in tissues.The time versus plasma concentration relationships of NFLX were analysed by means of PCNONLIN computer program (SCI, version 4.1, U.S.A.) using a weighted least squares regression analysis. Compartment model selection was based on visual inspection of the fit and use of the correlation between the observed and the calculated concentrations. The AUC from zero to infinity was determined using the linear trapezoidal rule. The bioavailability (F) was calculated with the formula: F=AUC oral /AUC i.v. * 100%. The pharmacokinetic parameters are reported as mean ± SEM. Mean pharmacokinetic parameters for NFLX, NFLXN and NFLXGA obtained after their oral administration were statistically compared by ANOVA analysis using PHARM/ PCS statistic program (version 4.0). The differences were considered to be significant at p<0.05.NFLX concentration-time data in all tested drugs were best fitted as a two compartment open models described by a bi-exponential expression with a rapid distribution and a rapid elimination phase, irrespective of the administration routes (Fig. 1). By this model, the pharmacokinetic parameters were obtained and listed in ABSTRACT. The pharmacokinetics and tissue distribution of two norfloxacin (NFLX) formulations, norfloxacin-glycine acetate (NFLXGA) and norfloxacin nicotinate (NFLXN), were compared after single oral administration with a dose of 5 mg equivalent NFLX base/kg of body weight in twenty rabbits. The pharmacokinetic characteristics of all formulations were fitted by a two-compartment open model. The elimination half-life (T 1/2β ) of NFLX (3.37 ± 1.37 hr) was not significant as compared with those of NFLXN (3.61 ± 0.65 hr) and NFLXGA (3.93 ± 1.54 hr). The absolute bioavailability (F) of NFLX, NFLXN and NFLXGA was calculated as 29%, 45% and 40%. In addition, tissue distribution of NFLXN and NFLXGA did not show any differences of NFLX concentrations in liver, kidney, serum and muscle. From the present results, it could be suggested that NFLXN and NFLXGA are considered to be bioequivalent when they use oral medication for rabbits.-KEY WORDS: bioavailability, norfloxacin, rabbit.

Modification of pharmacokinetics of norfloxacin following oral administration of curcumin in rabbits

“…The observed plasma concentration-time profile of norfloxacin was best described by the one compartment open model. The plasma levels of norfloxacin (group-I) at different time intervals were comparable to previous studies in rabbits receiving a similar dose [19], however, the plasma half-life was relatively short [14]. The increased plasma levels of norfloxacin observed in the present study (group-II) may be due to the by-pass of glucuronidation process in the intestine since curcumin was reported to suppress UDP-glucuronyltransferase levels in intestine and hepatic tissue [4].…”

“…Pharmacokinetic studies on norfloxacin in rabbits are limited [14,19]. The absorption of norfloxacin from gastrointestinal tract is limited [5,9].…”

Clinical pharmacokinetics of norfloxacin-glycine acetate after intravenous and oral administration in pigs

“…The amount of norfloxacin was measured by high performance liquid chromatography (HPLC) using the method described previously by Park et al [18]. Briefly, 1 ml serum was deproteinated with 1 ml 20% cold trichloroacetic acid in methanol.…”

“…The optimal dose range of the drug has been suggested to be 5-22 mg/kg body weight in these animals, on the basis of the minimal inhibition concentration (MIC) and the maximal norfloxacin concentration (C max ) in blood following drug administration. In our previous studies, we reported the pharmacokinetics of NFLXGA in flounder [16], horse [17] and rabbits [18]. …”

Bioavailability pharmacokinetics and residues of marbofloxacin in normal and E.coli infected broiler chicken

“…Fluoroquinolones are picking up ubiquity as imperative antibacterial agents in veterinary practice because of their broad antimicrobial activity (Park et al, 1998). Quinolones are dynamic against gram negative and gram positive microscopic organisms in vitro (Wolfson and Hooper, 1985), and in addition trimethoprim/sulfonamide resistant microbes (Preheim et al, 1987).…”