Pyrrole and Fused Pyrrole Compounds with Bioactivity against Inflammatory Mediators.

A new series of pyrrolopyridines and pyrrolopyridopyrimidines have been synthesized from aminocyanopyrroles. The synthesized compounds have been characterized by FTIR, ¹H-NMR and mass spectroscopy. The final compounds have been screened for in vitro pro-inflammatory cytokine inhibitory and in vivo anti-inflammatory activity. The biological results revealed that among all tested compounds some fused pyrroles, namely the pyrrolopyridines 3i and 3l, show promising activity. A docking study of the active synthesized molecules confirmed the biological results and revealed a new binding pose in the COX-2 binding site.

Plasma and Tissue Disposition of Moxifloxacin in Japanese Quail ( Coturnix japonica ).

Plasma disposition and depletion of moxifloxacin were investigated in Japanese quail ( Coturnix japonica ) after single intravenous, intramuscular, and oral administration of 5 mg/kg and after intramuscular and oral administration of 5 mg/kg q24h for 5 consecutive days, respectively. Drug concentrations in plasma and tissues were measured by high-performance liquid chromatography with fluorescence detection. After intravenous injection, plasma drug concentration-time curves were best described by a 2-compartment open model. The decline in plasma drug concentration was biexponential with half-lives of 0.3 hours and 2.18 hours for distribution and elimination phases, respectively. Steady-state volume of distribution and total body clearance after intravenous administration were estimated to be 1.12 L/kg and 0.41 L/h per kilogram, respectively. After intramuscular and oral administration of moxifloxacin at the same dose, the peak plasma concentrations were 2.14 and 1.94 µg/mL and were obtained at 1.4 and 1.87 hours, respectively, and the elimination half-lives were 2.56 and 1.97 hours, respectively. The systemic bioavailabilities were 92.48% and 87.94%, respectively. Tissue levels after intramuscular and oral administration were highest in liver and kidneys, respectively, and decreased in the following order: plasma, lungs, and muscle. Moxifloxacin concentrations after intramuscular and oral administration were below the detection limit of the assay in tissues and plasma after 120 hours.

Analysis of 10 systemic pesticide residues in various baby foods using liquid chromatography-tandem mass spectrometry.

Ten systemic pesticides, comprising methomyl, thiamethoxam, acetamiprid, carbofuran, fosthiazate, metalaxyl, azoxystrobin, diethofencarb, propiconazole, and difenoconazole, were detected in 13 baby foods (cereals, boiled potatoes, fruit and milk) using QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) for sample preparation and liquid chromatography tandem mass spectrometry for analysis. The matrix-matched calibration curves showed good linearity with determination coefficients (R(2) ) >0.992. The limits of detection and quantitation were 0.0015-0.003 and 0.005-0.01 mg/kg, respectively. The mean recoveries of three different concentrations ranged from 69.2 to 127.1% with relative standard deviations <20%. The method was successfully applied to 13 actual samples collected from a local market, and none of the samples were found to contain pesticide residues. This method is suitable for the identification and quantification of systemic pesticides with matrix-matched standards in various baby foods.

Optimization of supercritical fluid extraction method for detection of fluquinconazole and tetraconazole in soil using gas chromatography and confirmation using GC-MS: application to dissipation kinetics.

The aim of this study was to establish an analytical method to detect fluquinconazole and tetraconazole in soil using supercritical fluid extraction (SFE) and gas chromatography (GC). The optimal extraction conditions for SFE were: temperature, 60 °C; pressure, 280 kg/cm(2) ; extraction time, 50 min; and a 10% modifier ratio. The linearity of the calibration curves was good and yielded a determination coefficient (R(2) ) ≥ 0.995. The soil samples were fortified with known quantities of the analytes at three different concentrations (0.01, 0.02 and 0.1 µg/g for fluquinconazole; 0.05, 0.1 and 0.5 µg/g for tetraconazole), and the recoveries ranged between 83.7 and 94.1%. The intra- and inter-day relative standard deviations were 1.3-10.6 and 2.2-11.9% for fluquinconazole and tetraconazole, respectively. The limit of detection and limit of quantitation were 0.002 and 0.01 µg/g for fluquinconazole and 0.01 and 0.05 for tetraconazole, respectively. The method was successfully applied to the analysis of soil residues collected from an onion field. The results show that a combination of SFE and GC can be used as an environmentally friendly technique to detect fungicides in soil.

Cellular influx, efflux, and anabolism of 3-carboranyl thymidine analogs: potential boron delivery agents for neutron capture therapy.

3-[5-{2-(2,3-Dihydroxyprop-1-yl)-o-carboran-1-yl}pentan-1-yl]thymidine (N5-2OH) is a first generation 3-carboranyl thymidine analog (3CTA) that has been intensively studied as a boron-10 ((10)B) delivery agent for neutron capture therapy (NCT). N5-2OH is an excellent substrate of thymidine kinase 1 and its favorable biodistribution profile in rodents led to successful preclinical NCT of rats bearing intracerebral RG2 glioma. The present study explored cellular influx and efflux mechanisms of N5-2OH, as well as its intracellular anabolism beyond the monophosphate level. N5-2OH entered cultured human CCRF-CEM cells via passive diffusion, whereas the multidrug resistance-associated protein 4 appeared to be a major mediator of N5-2OH monophosphate efflux. N5-2OH was effectively monophosphorylated in cultured murine L929 [thymidine kinase 1 (TK1(+))] cells whereas formation of N5-2OH monophosphate was markedly lower in L929 (TK1(-)) cell variants. Further metabolism to the di- and triphosphate forms was not observed in any of the cell lines. Regardless of monophosphorylation, parental N5-2OH was the major intracellular component in both TK1(+) and TK1(-) cells. Phosphate transfer experiments with enzyme preparations showed that N5-2OH monophosphate, as well as the monophosphate of a second 3-carboranyl thymidine analog [3-[5-(o-carboran-1-yl)pentan-1-yl]thymidine (N5)], were not substrates of thymidine monophosphate kinase. Surprisingly, N5-diphosphate was phosphorylated by nucleoside diphosphate kinase although N5-triphosphate apparently was not a substrate of DNA polymerase. Our results provide valuable information on the cellular metabolism and pharmacokinetic profile of 3-carboranyl thymidine analogs.

Synthesis, biological evaluation, and radioiodination of halogenated closo-carboranylthymidine analogues.

The synthesis and initial biological evaluation of 3-carboranylthymidine analogues (3CTAs) that are (radio)halogenated at the closo-carborane cluster are described. Radiohalogenated 3CTAs have the potential to be used in the radiotherapy and imaging of cancer because they may be selectively entrapped in tumor cells through monophosphorylation by human thymidine kinase 1 (hTK1). Two strategies for the synthesis of a (127)I-labeled form of a specific 3CTA, previously designated as N5, are described: (1) direct iodination of N5 with iodine monochloride and aluminum chloride to obtain N5-(127)I and (2) initial monoiodination of o-carborane to 9-iodo-o-carborane followed by its functionalization to N5-(127)I. The former strategy produced N5-(127)I in low yields along with di-, tri-, and tetraiodinated N5 as well as decomposition products, whereas the latter method produced only N5-(127)I in high yields. N5-(127)I was subjected to nucleophilic halogen- and isotope-exchange reactions using Na(79/81)Br and Na(125)I, respectively, in the presence of Herrmann's catalyst to obtain N5-(79/81)Br and N5-(125)I, respectively. Two intermediate products formed using the second strategy, 1-(tert-butyldimethylsilyl)-9-iodo-o-carborane and 1-(tert-butyldimethylsilyl)-12-iodo-o-carborane, were subjected to X-ray diffraction studies to confirm that substitution at a single carbon atom of 9-iodo-o-carborane resulted in the formation of two structural isomers. To the best of our knowledge, this is the first report of halogen- and isotope-exchange reactions of B-halocarboranes that have been conjugated to a complex biomolecule. Human TK1 phosphorylation rates of N5, N5-(127)I, and N5-(79/81)Br ranged from 38.0% to 29.6% relative to that of thymidine, the endogenous hTK1 substrate. The in vitro uptake of N5, N5-(127)I, and N5-(79/81)Br in L929 TK1(+) cells was 2.0, 1.8, and 1.4 times greater than that in L929 TK1(-) cells.

Influence of endotoxin induced fever on the pharmacokinetics of intramuscularly administered cefepime in rabbits.

This study examined the effect of experimentally induced fever on the pharmacokinetics of cefepime (75 mg/kg BW) administered intramuscularly to six rabbits. The study was carried out in two consecutive phases separated by a two-week washout period. An infection was induced by an intravenous inoculation of 5 x 10(8) colony-forming units of Escherichia coli 24 h before the pharmacokinetic investigation. A quantitative microbiological assay was employed to measure the plasma cefepime concentrations using an agar-gel diffusion method with Bacillus subtilis ATCC 6633 as the test organism. Twenty-four hour after the injection, the rectal temperature in the infected animals increased by 1 degrees C. There was a significant reduction in the elimination halflife by 21.8 % in the febrile rabbits compared to healthy animals. In addition, the infection significantly increased the peak plasma concentrations by 11.9 %, the mean residence time by 19.9 %, the area under the plasmaconcentration-time curve by 53.6 % and the area under the moment curve by 62.3 %. In conclusion, the endotoxin-induced febrile state produced significant changes in the plasma levels as well as some of the pharmacokinetic variables of cefepime in rabbits.

Novel 4- Aryl-2(1H)-phthalazinone Derivatives as Cyclooxygenase-2 Inhibitors: Synthesis, Molecular Modeling Study and Evaluation as Promising Anti-inflammatory Agents.

BACKGROUND: Inflammation is a natural reaction of our body in response to infection or any other injury to renovate that damage. The majority of the available Non-steroidal anti-inflammatory drugs is nonselective and consequently, causes gastric irritation and ulceration. Therefore, it is a beard to design and synthesize a new series of Non-steroidal anti-inflammatory drugs with minimal gastric complications. METHODS: A series of novel 4-(3,4-dimethylphenyl)-2(1H)-phthalazinone derivatives were designed, synthesized and evaluated for their in vivo anti-inflammatory activity. The compounds that showed powerful anti-inflammatory activities were assessed for their in vitro COX-1/COX-2 inhibitory activity and their in vivo ulcerogenic profile. The interaction between the designated compounds and the binding pocket of the COX-2 enzyme was predicted by molecular docking stimulation. RESULTS: Six compounds, 2, 4, 5, 7a, 7b, and 8b showed significant anti-inflammatory activities at 4h compared to standard drug celecoxib. Compounds 4, 5, and 8b were the most potent and selective COX-2 inhibitors. Moreover, all the screened compounds demonstrated higher gastric safety profile compared to celecoxib particularly compound 8b displayed the highest safety profile. Among the tested compounds, 8b displayed the best fitting score, the highest antiinflammatory activity and COX-2 selectivity with minimal ulcer score. CONCLUSION: A new series of phthalazinone derivatives were successfully synthesized and were evaluated for their in vivo anti-inflammatory activity. Six compounds (2, 4, 5, 7a, 7b, and 8b) presented powerful anti-inflammatory activity compared to celecoxib. Moreover, compounds 4, 5 and 8b were the most potent inhibitors to COX-2 and were inactive to COX-1. The screened compounds showed better ulcer protection and less gastric lesion compared to celecoxib. Compound 8b was the most promising candidate with more gastric safety.

Acute and subchronic toxicity assessment model of Ferula assa-foetida gum in rodents.

AIM: The present study was performed to investigate acute and subchronic oral toxicity of Ferula assa-foetida gum (28 days) in Sprague Dawley rats. MATERIALS AND METHODS: Acute oral administration of F. assa-foetida was done as a single bolus dose up to 5 g/kg in mice and subchronic toxicity study for 28 days was done by oral administration at doses of 0 (control) and 250 mg/kg in Sprague Dawley rats. RESULTS: The obtained data revealed that oral administration of F. assa-foetida extract in rats for 28 successive days had no significant changes on body weight, body weight gain, the hematological parameters in rats all over the period of the experiment, and there are no significant increases in the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. Liver of treated rats showed mild changes as thrombosis and sinusoidal leukocytosis. It also showed portal infiltration with inflammatory cells, while kidney of treated rat showed an atrophy of glomerular tuft, thickening of parietal layer of Bowman capsule, and focal tubular necrosis. It also showed dilatation and congestion of renal blood vessels. CONCLUSION: We concluded that F. assa-foetida gum had broad safety and little toxicity for short term use in dose of 250 mg/kg.

Pharmacokinetics and distribution of ceftazidime to milk after intravenous and intramuscular administration to lactating female dromedary camels (Camelus dromedarius).

OBJECTIVE: To determine the plasma disposition kinetics, absolute bioavailability, and milk concentrations of ceftazidime in healthy lactating female dromedary camels (Camelus dromedarius) following IV and IM administration of a single dose of 10 mg/kg (4.5 mg/lb). DESIGN: Prospective crossover study. ANIMALS: 8 healthy adult lactating female dromedary camels. PROCEDURES: Camels received ceftazidime (10 mg/kg) IV and IM in a crossover study design with a 15-day washout period between treatments. Plasma and milk samples were collected at predetermined times for 48 hours after drug administration and analyzed by use of high-performance liquid chromatography. RESULTS: A 2-compartment open model best represented the plasma concentration-versus-time data after IV and IM administration of ceftazidime to camels. Plasma ceftazidime concentrations decreased biexponentially after IV administration with mean distribution and elimination half-lives of 0.3 hours and 2.85 hours, respectively. After IM administration, the mean maximum plasma concentration of ceftazidime was 32.43 µg/mL (1.21 hours after administration), mean elimination half-life was 3.20 hours, mean residence time was 4.84 hours, and mean systemic bioavailability was 93.72%. Distribution of ceftazidime from plasma to milk was rapid and extensive as indicated by the ratio of the area under the milk concentration-versus-time curve to the area under the plasma concentration-versus-time curve and the ratio of the maximum milk concentration to the maximum plasma concentration of ceftazidime after IV and IM administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that ceftazidime may be a useful treatment for female camels with mastitis caused by susceptible microorganisms.

Synthesis, chemical and enzymatic hydrolysis, and aqueous solubility of amino acid ester prodrugs of 3-carboranyl thymidine analogs for boron neutron capture therapy of brain tumors.

Various water-soluble L-valine-, L-glutamate-, and glycine ester prodrugs of two 3-Carboranyl Thymidine Analogs (3-CTAs), designated N5 and N5-2OH, were synthesized for Boron Neutron Capture Therapy (BNCT) of brain tumors since the water solubilities of the parental compounds proved to be insufficient in preclinical studies. The amino acid ester prodrugs were prepared and stored as hydrochloride salts. The water solubilities of these amino acid ester prodrugs, evaluated in phosphate buffered saline (PBS) at pH 5, pH 6 and pH 7.4, improved 48-6600 times compared with parental N5 and N5-2OH. The stability of the amino acid ester prodrugs was evaluated in PBS at pH 7.4, Bovine serum, and Bovine cerebrospinal fluid (CSF). The rate of the hydrolysis in all three incubation media depended primarily on the amino acid promoiety and, to a lesser extend, on the site of esterification at the deoxyribose portion of the 3-CTAs. In general, 3'-amino acid ester prodrugs were less sensitive to chemical and enzymatic hydrolysis than 5'-amino acid ester prodrugs and the stabilities of the latter decreased in the following order: 5'-valine > 5'-glutamate > 5'-glycine. The rate of the hydrolysis of the 5'-amino acid ester prodrugs in Bovine CSF was overall higher than in PBS and somewhat lower than in Bovine serum. Overall, 5'-glutamate ester prodrug of N5 and the 5'-glycine ester prodrugs of N5 and N5-2OH appeared to be the most promising candidates for preclinical BNCT studies.

Disposition kinetics of levofloxacin in sheep after intravenous and intramuscular administration.

The present study was planned to investigate the disposition kinetics of levofloxacin in plasma of female native Barky breed sheep after single intravenous (IV) and intramuscular (IM) administration of 4 mg/kg body weight. The concentrations of levofloxacin in the plasma were measured using high-performance liquid chromatography (HPLC) with a UV detector on samples collected at 0, 0.08, 0.16, 0.33, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 32, and 48 h after treatment. Following intravenous injection, the decline in plasma drug concentration was biexponential with half-lives of (t(1/2α)) 0.33 ± 0.12 h and (t(1/2ß)) 3.29 ± 0.23 h for distribution and elimination phases, respectively. The volume of distribution at steady state V((d(ss))) was 0.86 ± 0.23 l/kg. After intramuscular administration of levofloxacin at the same dose, the peak plasma concentration (C(max)) was 3.1 ± 0.35 µg/mL and was obtained at 1.64 ± 0.29 h (T(max)), the elimination half-life (T(1/2el)) was 3.58 ± 0.30 h, and AUC was 20.24 ± 1.31 µg.h/mL. The systemic bioavailability was 91.35 ± 6.81 %. In vitro plasma protein binding was 23.74%. When approved therapy fails, levofloxacin may be used in some countries for therapy of food animals, however, that is not true in the US.

Approaches for application of sub and supercritical fluid extraction for quantification of orbifloxacin from plasma and milk: application to disposition kinetics.

Since its extensive development in the early 1980s, SFE has attracted considerable attention as a sample-preparation procedure. However, other different sample preparation procedures, including precipitation, liquid- and/or solid-phase extraction in biological fluids, also remain in use. In this investigation, SFE was introduced to isolate and identify orbifloxacin from plasma and milk. Four parameters, including the temperature and the pressure of supercritical fluid, modifier ratios, and dynamic extraction time, were evaluated and optimized to obtain the best yield of the analyte from the biological fluids. Determinations of the orbifloxacin (OBFX) in the extracts were carried out using HPLC-FLD. The optimum conditions of the extraction process that yielded the maximum analyte extraction efficiencies were 150 degrees C vs. 60 degrees C, 250 kg cm(-2), 30% vs. 35% methanol, and 40 min vs. 20 min, for plasma and milk, respectively. The linearity of the calibration curves as well as the instrument LODs/LOQs were evaluated. Good linearity (at least r(2) > or = 0.999) of the calibration curves was obtained over the range from 0.2 to 0.01 microg mL(-1). The method showed a good recovery rate (74.2-127.73%) and precision (RSDs: 1.64-20%). The instrumental LOD and LOQ values were 0.004 microg mL(-1) vs. 0.01 microg mL(-1) or 0.006 microg mL(-1) vs. 0.02 microg mL(-1), for plasma and milk, respectively. The method was successfully applied to estimate the pharmacokinetic variables of orbifloxacin in lactating does. To the best of our knowledge, this is the first time that SFE has been applied to isolate an antimicrobial agent from biological fluids. This method is promising for clinical applications and for pharmacokinetic studies of various pharmaceuticals in biological fluids.

Concentration-time courses of pefloxacin in plasma and milk of lactating she-camels (Camelus dromedarius).

Using the microbial inhibition test, the single-dose pharmacokinetics of pefloxacin mesylate dehydrate were studied in six clinically normal lactating she-camels (Camelus dromedarius) after intravenous (IV) and intramuscular (IM) administration of 10 mg/kg body weight (bwt). Blood and milk samples were collected intermittently for a 48 h period, and the pharmacokinetic variables were calculated using compartmental and non-compartmental analytical methods.The plasma course of pefloxacin was best resolved to a two-compartment open model after IV administration and a two-compartment open model with first-order absorption after IM administration. Pefloxacin exhibits a long elimination-phase disposition half-life (t1/2beta) of 4.89 +/- 1.12 h after IV injection and 5.73 +/- 1.42 h after IM administration. The mean volume of distribution at steady state (Vdss) and total body clearance (Cl(tot)) values after IV dosing were 1.18 +/- 0.45 I/kg and 0.21 +/- 0.10 I/kg/h, respectively. The observed peak plasma level (Cmax) of 3.6 +/- 0.1 microg/ml was rapidly attained at 0.75 h (the time of maximum concentration Tmax) after IM administration. The areas under the concentration versus time curves (AUCs) were 44.18 +/- 9.68 microg x h/ml and 29.42 +/-6.49 microg x h/ml after IV and IM administration, respectively. The absolute bioavailability (F%) obtained after IM administration was 71.59 +/- 12.45%. Milk was penetrated quickly, with a mean peak level of 3.24 +/- 0.17 microg/ml occurring at 1.0 h. The elimination half-life was significantly shorter after IV versus IM administration (4.21 +/- 0.84 h versus 5.32 +/- 0.67 h, respectively). Ultimately, pefloxacin could be useful for treatment of udder infections in she-camels after specific assessment of susceptible microorganisms.

Development of extraction procedures for the determination of imidacloprid: application to residue analysis and dynamics of two formulations in Chinese cabbage.

This study was undertaken to investigate whether an additional column clean-up procedure can affect the accuracy of an analytical method developed for the determination of imidacloprid residues in Chinese cabbage. Thereafter, the residue levels and the degradation rates of imidacloprid were investigated in experimental Chinese cabbage plots after treatment with two different commercial formulations: emulsifiable concentrate (EC) and wettable powder (WP). The analyte was determined using high-performance liquid chromatography-ultraviolet detection (HPLC-UVD) and confirmed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) in the select ion-monitoring mode. The mean recoveries ranged from 75.34 to 98.00% and 96.95 to 100.97%, with relative standard deviations of 0.86-4.14 and 1.22-3.52%, in samples treated with and without additional column clean-up procedures, respectively. The minimum detectable amount of imidacloprid was 4 ng, while the limits of detection and quantitation were 0.2 and 0.5 ppm, respectively. The degradation of pesticide was monitored throughout a period of 13 days under greenhouse conditions. Although the behaviors of the EC and WP formulations appear to be similar, the absolute residue levels obtained with EC and WP treatments differed slightly. When imidacloprid formulations were applied (as foliar treatments) according to the recommended rate, the final residues (13 days post-treatment) in Chinese cabbage were much lower than the maximum residue limit (MRL = 3.5 ppm) established by the Korean Food and Drug Administration. Taken together, our study suggests that the analysis of imidacloprid can be performed without an additional column clean-up procedure, and the decline curve and the residue levels in Chinese cabbage could change if the same active ingredient is used in different formulations.

Monitoring of fluoroquinolone residual levels in chicken eggs by microbiological assay and confirmation by liquid chromatography.

The primary objective of this study was to develop a simple, rapid, and efficient method for the simultaneous determination of four fluoroquinolone residues, ciprofloxacin (CFX), danofloxacin (DFX), enrofloxacin (EFX) and norfloxacin (NFX), in chicken eggs. The samples were first monitored by microbiological assay using Escherichia coli as the reference organism, and were then quantified using HPLC with a fluorescence detector. Egg samples were extracted by the liquid-phase extraction process, and the analytes were analyzed via an ODS column using a mixture of acetonitrile and 0.4% phosphoric acid-0.4% triethylamine (15: 85, v/v) as a mobile phase (pH=2) without purification. The calibration curves were linear (r2>or=0.999) over a concentration range of 0.1-1.0 microg/mL. The majority of the mean recoveries at four different fortification levels, 0.1, 0.2, 0.5 and 1.0 ppm, ranged from 73.7+/-7.2% to 87.1+/-12.7%, and the repeatability (as the relative standard deviation) from three repetitive determinations of recovery was between 1.03 and 18.83%. The calculated limit of quantitation (LOQ) was 9 ppb for CFX, EFX and NFX and 0.6 ppb for DFX. Both the bioassay and HPLC methods were applied to 120 total egg samples collected from the six major cities in the Republic of Korea. The bioassay, showed that two samples were positive (i.e contained inhibiting substances). On the other hand, the results of HPLC only identified and quantified the residues of enrofloxacin (from 0.43 to 1.02 ppm) in three samples out of 120. We concluded that the bioassay can be used as a routine screening method for the presence of fluoroquinolones in chicken eggs, which can be confirmed and quantified using LC.

Single-dose pharmacokinetics of marbofloxacin in Egyptian buffalo (Bubalus bubalis L.) steers.

The objective of this study was to investigate the pharmacokinetics of marbofloxacin (MAR) following intravenous (iv) and intramuscular (im) administration of a 2.0 mg/kg body weight dosage to five healthy Egyptian buffalo steers. A cross-over design was used with a washout period of 2 weeks. Blood samples were obtained at 0, 5,10,15, and 20 min and at 0.5,0.75,1,2,4,6,8,10,12,24,30 and 48 hours after marbofloxacin administration. The serum marbofloxacin concentrations were quantitated using a modified agar diffusion bioassay method. Marbofloxacin exhibited a relatively high volume of distribution at steady-state (Vdss = 1.77 Lkg), which suggests good tissue penetration, and a total body clearance (Cltot) of 0.18 L/kgxh,which is associated with a long elimination half-life (tl/2beta = 7.52 h). Marbofloxacin was rapidly absorbed at a dosage of 2.0 mg/kg after im administration with an observed maximum serum concentration (Cmax) value of 2.004 microg/mL obtained at a time to peak concentration (tmax) of 0.5 h, and an absolute bioavailability (F %) of 86.79 +/- 5.53 %. The protein-binding ranged from 22 to 24.6 % with an average of 23.4 %. In conclusion, single iv and im administered doses of marbofloxacin were well tolerated by Egyptian buffalo steers. A dosage of 2 mg/kg body weight might not be enough to treat infections caused by bacteria with minimum inhibitory concentration (MIC) at or above 0.2 microg/mL, based on the calculated area under the inhibitory concentration (AUIC).