Bioavailability Of Ofloxacin Research Articles

Pharmacokinetics and bioavailability of ofloxacin following single intramuscular and subcutaneous administration in goats

Comparative disposition kinetics of ofloxacin following intramuscular (i.m.) and subcutaneous (s.c.) administration was studied in goats @ 10 mg/kg. Ofloxacin was determined by HPLC method and kinetic parameters using a software. Appreciable plasma concentrations were observed within 2.5 min of drug administration and peaked at 1 h. t1/2ka and t1/2β values were 13.59 and 78.41 min after i.m. administration while 17.89 and 103.59 min after s.c. administration and the corresponding bioavailability values were 75.43±5.00 and 102.07±7.00 %. Ofloxacin may be adiministered to goat @10 mg/kg at 12 h interval by s.c. route.

COMPARATIVE STUDY OF PHARMACOKINETICS OF OFLOXACIN IN A FREE AND NIOSOMAL FORMS IN EXPERIMENTS ON WHITE MICE WHEN ADMINISTERED Per Os

Aim: to study features of pharmacokinetics of ofloxacin as a part of anion PEGylated niosomes on a basis of sorbitan monostearate (Span 60) to experimental white mice per os. Materials and methods: ofloxacin was entrapped in niosomes consisting of Span 60, cholesterol, PEG 4000 and dicetylphosphate. Sizes of niosomes estimated by means of probe microscopy. Efficiency of inclusion of an antibiotic in niosomes defined after removal of free drug by a centrifugation. The analysis of the quantitative contents of ofloxacin in samples carried out a method of a high performance liquid chromatography. Results: we studied the main pharmacokinetic parameters of ofloxacin when used free and niosomal forms of antibiotic to experimental white mice per os. It is shown that use of oral niosomal forms leads to decrease of maximal concentration in serum and increase of ofloxacin half-life by 7,4 times in average compared to the free form. It is determined that bioavailability of ofloxacin in the niosomal form is 154% relative to the free form of the antibiotic. Conclusions: niosomal microcontainers are perspective technology of encapsulation and the directed transport of antibacterial preparations through biological barriers. Using of niosomal formulation of ofloxacin is able to afford to increase considerably efficiency of treatment in comparison with a free form and significantly decrease negative effects of antibiotic therapy.

FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF OFLOXACIN BY DIRECT COMPRESSION METHOD

Ofloxacin is a broad - spectrum, synthetic fluoroquinolones antibacterial agent for oral administration. The bioavailability of ofloxacin in the tab let formulation is approximately 98 %. It is extremely bitter i n taste, wate r insoluble drug. It is used to treat variety of infections . The purpose of the present research work was to formulate and evaluate the fast dissolving tablets of ofloxacin by direct compression method using different super disintegrants like PGS (pre gela tinized starch), SSG (sodium starch glycolate), PVPP (ploy vinyl poly pyrrolidone) in different concentrations 5 %, 7.5 %, 10 %. FT - IRspectroscopy was used to investigate the physical characteristics of the complex. The blend was evaluated for angle of rep ose, bulk density, tapped density, carr’s index, hausner ratio. The tablets were evaluated for weight v ariation, hardness, friability, disintegration time, water absorption ratio, wetting time, drug content uniformity and in vitro dissolution. Tablet formu lated with 10 % (F 9 ) of PVPP showed low disintegration time (8 ± 2), wetting time (4.3 ± 0.3), friability than the other batches. The % cumulative release of drug from tablet (F 9 ) was found to be more than 87 % within 10 min ute s. It was concluded from the study that ofloxacin may improve patient compliance especially pediatric and geriatric patients and increase the efficacy of drug for treating inf ections.

Design and Development of Novel Dual-Compartment Capsule for Improved Gastroretention

The aim of the proposed research work was to develop a novel dual-compartment capsule (NDCC) with polymeric disc for gastroretentive dosage form, which will ultimately result in better solubility and bioavailability of Ofloxacin. Floating ring caps were formulated by using different natural polymers, separating ring band and swellable polymer located at the bottom of capsule. Formulated ring caps were assessed for coating thickness, In vitro buoyancy, In vitro drug release, release kinetics and stability studies. Coating attained by the capsule shell was found to be 0.0643 mm. Depending on nature of natural polymer used, most of the formulations showed buoyancy for more than 9 hrs. Developed formulation demonstrated considerably higher drug release up to 9 hrs. The developed formulation FE2 depicted the drug release according to Korsmeyer-Peppas model. There was not any significant change in performance characteristics of developed ring caps after subjecting them to stability studies. The present study suggests that the use of NDCC for oral delivery of Ofloxacin could be an alternative to improve its systemic availability which could be regulated by the floating approach. The designed dosage system can have futuristic applications over payloads which require stomach-specific delivery.

Effects of hepatic fibrosis on ofloxacin pharmacokinetics in rats

The purpose of the present work was to study the pharmacokinetics of ofloxacin, a poorly metabolised drug, in experimental hepatic fibrosis. The possible roles of small intestinal P-glycoprotein (P-gp) and cytochrome P450 (CYP) in the bioavailability of ofloxacin were also evaluated. Rat hepatic fibrosis model was successfully induced using complex factors including carbon tetrachloride, ethanol and high fat. After rats received a single oral or intravenous dose of ofloxacin (40 mg kg −1), the plasma concentrations of ofloxacin were monitored at the scheduled time using spectrofluorimetric assay. Plasma concentration–time profiles were comodeled using compartmental method. Meanwhile, microsomal CYP isoenzymatic levels and P-gp expression in small intestines were compared between normal and hepatic fibrosis rats. When ofloxacin was administered intravenously, C max and the distribution half-life increased significantly in comparison with normal group, whereas the distribution rate constants, the apparent volume of distribution decreased. Oral ofloxacin bioavailability was significantly altered in hepatic fibrosis rats. AUC and C max were reduced, while the absorption half-life, peak time and elimination half-life significantly were prolonged, suggesting that both the extent and the rate of ofloxacin absorption were decreased. Furthermore, the increases in the levels of microsomal ethoxyresorufin O-deethylase and erythromycin N-demethylase were accompanied with up-regulation of mdr 1a mRNA in the small intestines of hepatic fibrosis rats when compared to those of the normal rats. The Results showed that pharmacokinetics of ofloxacin could be altered in hepatic fibrosis. Up-regulated P-gp expression and increased CYP isoenzymatic activities of small intestines in hepatic fibrosis rats may contribute to the decreased bioavailability and increased elimination of ofloxacin after oral administration.

EFFECTS OF EXPERIMENTALLY INDUCED COLIBACILLOSIS ON THE PHARMACOKINETICS OF OFLOXACIN IN CHICKENS

Colibacillosis was produced experimentally in 14 white Leghorn broiler chickens by intratracheal inoculation of 0.3 ml broth of E. coli O78:K80 containing approximately 106 colony forming unit. Another 7 clinically normal chickens were used in this study. Ofloxacin was administered to chickens intravenously and orally (5 mg/kg b.wt.) to determine the effect of colibacillosis on its kinetic behavior. The concentration of ofloxacin in serum samples collected at presche-duled time were estimated by using microbiological assay. The phar-macokinetic parameters were determined by two compartment open model. The drug concentration (≥ 0.1 µg/ml) was maintained up to 24 h. There were statistically (P<0.05) significant differences between normal and colibacillosed chickens represented by half-time of elimin-ation,transfer rate constants,elimination rate constant,apparent volume of the central compartment and body clearance of the drug following intravenous administration. Following oral administration the absorp-tion rate constant, absorption half-life and the time needed to reach the maximum concentration were statistically (P<0.05) significantly diffe-rent between normal and colibacillosed chickens. The bioavailability of ofloxacin in normal chickens following oral administration was found to be 91.9 ± 8.25%. The in vitro protein binding of ofloxacin in normal chicken serum at different concentrat-ions was 15.98 ± 0.92%. Based on these kinetic parameters clinical application of ofloxacin at a dose of 5 mg/kg at 24 h dosing interval by intravenous or oral administration in chickens is recommended.

Probenecid Affects the Pharmacokinetics of Ofloxacin in Healthy Volunteers

The aim of this randomised, double-blind, crossover study was to evaluate the effect of single-dose probenecid on the pharmacokinetics of ofloxacin in eight healthy male volunteers. After an overnight fast, and according to a randomised sequence, each volunteer received either single oral ofloxacin 200mg (Hoechst Marion Roussel Ltd., Mumbai, India) or both ofloxacin (1 x 200mg) and probenecid (1 x 500mg) [Geno Pharmaceutical Ltd., Mumbai, India]. Blood samples were collected at regular intervals until 24 hours. Serum concentration versus time profiles for ofloxacin were generated and pharmacokinetic parameters were calculated by noncompartmental model analysis. Elimination half-life, mean residence time and area under the curve were significantly increased (4.86 vs 5.26h; 7.23 vs 7.95h; 10.28 vs 11.9 mg/L . h) [p < 0.01], whereas the total clearance was decreased (19.66 vs 16.95 L/h) [p < 0.01] in the presence of probenecid. Other pharmacokinetic parameters were not significantly affected by coadministration of probenecid. Concomitant administration of probenecid with ofloxacin may result in a decreased elimination half-life and consequently increased bioavailability of ofloxacin. Probenecid may be co-prescribed with ofloxacin; patients taking this combination should be closely monitored and dosage reduction should be considered if warranted in high-risk patients.

Effects of aluminium-containing antacid on bioavailability of ofloxacin following oral administration of pivaloyloxymethyl ester of ofloxacin as prodrug.

We newly synthesized a pivaloyloxymethyl ester of ofloxacin (OFLX-PVM) as prodrug in order to avoid the chelate formation between new quinolone and metal cations such as Al3+, Mg2+, Ca2+, or Fe2+ in the gastrointestinal tract. This compound was rapidly hydrolyzed in an incubation experiment by 43% in plasma, by 92% in small intestinal mucosal homogenates, and by 97% in liver homogenates during 0.5 h incubation, but was resistant to hydrolysis by pancreatic enzymes. In everted gut sac experiments, this compound was efficiently absorbed even in the presence of aluminium ion, whereas the absorption of ofloxacin (OFLX) was decreased significantly by the presence of aluminium ion. Minimal inhibitory concentration (MIC) values of OFLX-PVM were far higher than OFLX. Effects of aluminium hydroxide on the oral bioavailability of OFLX and OFLX-PVM were investigated in rabbits. The area under the plasma concentration-versus-time curve from zero to 24 h (AUC0-24h) following oral administration of OFLX was decreased significantly by 47.6% by combined administration with aluminium hydroxide, but AUC0-24h values of OFLX-PVM coadministered with and without aluminium hydroxide were similar to that of OFLX alone. These observations indicate that this new compound is likely to offer a prodrug for avoidance of interaction between new quinolone and metal cations.

The bioavailability of ofloxacin from several formulations

The bioavailability of ofloxacin after a single dose of one of two tablet formulations (200 or 400 mg) or a liquid formulation (1.67 mg/ml) was investigated in 24 healthy male volunteers in an open randomized, crossover design study with a 5-day wash-out period between doses. Plasma concentrations of ofloxacin were determined at various times after administration by a sensitive and specific High Pressure Liquid Chromatography (HPLC) method. Ofloxacin was well absorbed after each administration, although somewhat more slowly after the tablet formulations than the solution. Mean AUC values of 31.8, 31.3, and 31.3 micrograms.hr/ml were calculated after administration of the solution, 2 x 200 mg tablets and a 400 mg tablet, respectively. Thus, the bioavailability of the tablets was in excess of 98% that of the liquid reference. Mean Cmax values of 4.4, 3.7 and 3.7 micrograms/ml were observed at Tmax values of 0.8, 1.6 and 1.8 hours after administration of the solution, 2 x 200 mg tablets and a 400 mg tablet, respectively. The drug was well tolerated and no adverse effects necessitating subject withdrawal were noted during the study.

Effects of magnesium-aluminum hydroxide and calcium carbonate antacids on bioavailability of ofloxacin

The effects of 15- and 5-ml doses of magnesium-aluminum hydroxide (MAH) and calcium carbonate (CC) antacids, respectively, on the bioavailability of ofloxacin after single oral 400-mg doses of ofloxacin were investigated in a 32-subject, randomized, crossover, open-label study. On four separate occasions, subjects received ofloxacin alone or antacid 24 h before, 2 h before, or 2 h after ofloxacin administration (n = 16 for each antacid). CC administration had no significant effect on the rate and extent of ofloxacin absorption regardless of the timing of antacid administration. A small but significant negative effect of MAH administration 2 h before ofloxacin administration was noted as evidenced by area under the curve and peak concentration in plasma data. Simultaneous administration of ofloxacin with either antacid was not investigated in this study. It appears that MAH and CC antacids in the doses used in this study generally do not interfere in a clinically significant manner with the bioavailability of ofloxacin, provided that an interval of at least 2 h separates the administration of these products.

Pharmacokinetic evaluation of ofloxacin in serum and tonsils.

The bioavailability of ofloxacin in tonsil tissue, after a single oral dose of 200 mg 2 h before surgery, was evaluated in 14 patients undergoing tonsillectomy for recurrent or chronic infection. A blood specimen was obtained just before drug administration and at the time of tonsillectomy, together with a specimen of tonsil tissue. The mean values of the serum and tonsil concentrations 2 h after a single dose of 200 mg were 1.17 mg/l +/- 0.47 and 1.61 mg/l +/- 0.62 respectively with a mean tonsil/serum ratio of 1.40 +/- 0.19. These values indicate good penetration of ofloxacin into tonsil tissue. No clinical or biological side-effects were observed.