The pharmacokinetic behaviour of marbofloxacin in Eurasian buzzards (Buteo buteo) after intraosseous administration

This study reports on the administration of a single dose of marbofloxacin (2 mg/kg) to five adult Eurasian buzzards (Buteo buteo) by the intraosseous (IO) route, which has been proposed as a rapid and efficient means for the parenteral delivery of antimicrobial drugs. The drug was rapidly absorbed. Peak marbofloxacin concentration (C(max)) in plasma and area under the concentration-time curve (AUC) of 1.92+/-0.78 microg/mL and 8.53+/-2.73 microg h/mL, respectively. The time marbofloxacin remained in the plasma after IO administration was relatively short (elimination half-life, t(1/2beta)=4.91+/-0.65 h; mean residence time (MRT)=5.38+/-0.57 h). Single dose marbofloxacin gave values for C(max)/minimum inhibitory concentration (MIC) of 19.2 and an AUC/MIC value of 85.3h after IO administration. The IO route appears to be practical and effective for the rapid delivery of marbofloxacin to buzzards.     

Pharmacokinetics of ceftazidime after intravenous and intramuscular administration to domestic cats

The pharmacokinetic properties of ceftazidime, a third generation cephalosporin, were investigated in five cats after single intravenous (IV) and intramuscular (IM) administration at a dose rate of 30 mg/kg. Minimum inhibitory concentrations (MICs) of ceftazidime for some Gram-negative (Escherichia coli, n=11) and Gram-positive (Staphylococcus spp., n=10) strains isolated from clinical cases were determined. An efficacy predictor, measured as the time over which the active drug exceeds the bacteria minimum inhibitory concentration (T>MIC), was calculated. Serum ceftazidime disposition was best fitted by a bi-compartmental and a mono-compartmental open model with first-order elimination after IV and IM dosing, respectively. After IV administration, distribution was rapid (t(1/2(d)) 0.04+/-0.03 h), with an area under the ceftazidime serum concentration:time curve (AUC((0-infinity))) of 173.14+/-48.69 microg h/mL and a volume of distribution (V((d(ss)))) of 0.18+/-0.04 L/kg. Furthermore, elimination was rapid with a plasma clearance of 0.19+/-0.08 L/hkg and a t(1/2) of 0.77+/-0.06 h. Peak serum concentration (C(max)), T(max), AUC((0-infinity)) and bioavailability for the IM administration were 89.42+/-12.15 microg/mL, 0.48+/-0.49 h, 192.68+/-65.28 microg h/mL and 82.47+/-14.37%, respectively. Ceftazidime MIC for E. coli ranged from 0.0625 to 32 microg/mL and for Staphylococcus spp. from 1 to 64 microg/mL. T>MIC was in the range 35-52% (IV) and 48-72% (IM) of the recommended dosing interval (8-12h) for bacteria with a MIC(90)4 microg/mL.     

Pharmacokinetics of marbofloxacin after single intravenous and repeat oral administration to cats

The pharmacokinetic properties of marbofloxacin, a third generation fluoroquinolone, were investigated in six cats after single intravenous (IV) and repeat oral (PO) administration at a daily dose of 2 mg/kg. Marbofloxacin serum concentration was analysed by microbiological assay using Klebsiella pneumoniae ATCC 10031 as micro-organism test. Serum marbofloxacin disposition was best described by bicompartmental and mono-compartmental open models with first-order elimination after IV and oral dosing respectively. After IV administration, distribution was rapid (T(1/2(d)) 0.23+/-0.24 h) and wide, as reflected by the steady-state volume of distribution of 1.01+/-0.15 L/kg. Elimination from the body was slow with a body clearance of 0.09+/-0.02 L/h kg and a T(1/2) of 7.98+/-0.57 h. After repeat oral administration, absorption half-life was 0.86+/-1.59 h and T(max) of 1.94+/-2.11 h. Bioavailability was almost complete (99+/-29%) with a peak plasma concentration at the steady-state of 1.97+/-0.61 mug/mL. Drug accumulation was not significant after six oral administrations. Calculation of efficacy predictors showed that marbofloxacin has good therapeutic profile against Gram-negative and Gram-positive bacteria with a MIC(50) value <0.25 microg/mL.     

Pharmacokinetic behavior and pharmacokinetic/pharmacodynamic integration of marbofloxacin after subcutaneous administration in goats

The pharmacokinetic behavior of marbofloxacin was studied in goats after single-dose subcutaneous (SC) administration of 2mg/kg bodyweight. Drug concentration in plasma was determined by high performance liquid chromatography and the data obtained were subjected to non-compartmental kinetic analysis. Marbofloxacin peak plasma concentration (C(max)=1.77+/-0.24microg/mL) was reached 1.25+/-0.50h (T(max)) after SC administration. The elimination half-life (t(1/2beta)) and area under curve (AUC) were 5.74+/-1.21h and 8.15 vs 2.33microg h/mL, respectively. Taking into account the values obtained for the efficacy indices, it was concluded that a SC dose of 2mg/kg/24h of marbofloxacin could be adequate to treat infections caused by high susceptible bacteria like Escherichia coli or Salmonella spp.     

Pharmacokinetics of marbofloxacin in blue and gold macaws (Ara ararauna)

OBJECTIVE: To determine the pharmacokinetics of marbofloxacin after single IV and orally administered doses in blue and gold macaws. ANIMALS: 10 healthy blue and gold macaws. PROCEDURES: In a crossover study, marbofloxacin (2.5 mg/kg) was administered orally (via crop gavage) to 5 birds and IV to 5 birds. Blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hours after marbofloxacin administration. After a 4-week washout period, the study was repeated, with the first 5 birds receiving the dose IV and the second 5 birds receiving the dose orally. Serum marbofloxacin concentrations were quantitated by use of a validated liquid chromatography-mass spectrometry assay. RESULTS: After oral administration, mean +/- SD area under the curve was 7.94 +/- 2.08 microg.h/mL, maximum plasma concentration was 1.08 +/- 0.316 microg/mL, and bioavailability was 90.0 +/- 31%. After IV administration of marbofloxacin, the apparent volume of distribution was 1.3 +/- 0.32 L/kg, plasma clearance was 0.29 +/- 0.078 L/h/kg, area under the curve was 9.41 +/- 2.84 microg.h/mL, and the harmonic mean terminal half-life was 4.3 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Single IV and orally administered doses of marbofloxacin were well tolerated by blue and gold macaws. The orally administered dose was well absorbed. Administration of marbofloxacin at a dosage of 2.5 mg/kg, PO, every 24 hours may be appropriate to control bacterial infections susceptible to marbofloxacin in this species.     

Pharmacokinetics and residues in milk of oxytetracyclines administered parenterally to dairy goats

OBJECTIVE: To determine for two commercial preparations of oxytetracycline (OTC) the pharmacokinetic behaviour, the presence of detectable milk residues and the penetration in milk of OTC administered by intravenous (IV) (conventional formulation [CF]) and intramuscular (IM) routes (CF and long-acting [LA] formulations) in goats producing milk. The effects of these formulations on plasma activity values of creatine kinase (CK) and lactate dehydrogenase (LDH) were also determined as indicators of tissue damage. PROCEDURE: Five healthy lactating goats producing 1.5+/-0.5 L/d milk and weighing 56.0+/-4.8 kg were used. Single doses of OTC chlorhydrate (CF) were administered (20 mg OTC/kg) by IV (Trial 1 IV) and IM (Trial 1 IM) routes and OTC dehydrate (LA) by the IM route. The same goats were first given IV CF, then IM CF followed by IM LA with 3 weeks between each treatment. Blood and milk samples were taken. The quantification of OTC was performed by HPLC and the plasma activities of CK and LDH enzymes were determined by spectrophotometry. The presence of OTC residues in milk was determined by a commercial reagent. The plasma pharmacokinetic parameters were calculated using a two-compartment model. RESULTS: Estimates of kinetic variables following IV administration were: Vss= 400.0+/-120.0 mL/kg and CL= 110.0+/-14.0 (mL/h)/kg. The t(fi) for IV= 3.0+/-0.3 h; IM, CF = 10.5+/-2.1 h and IM, LA = 15.1+/-3.1 h. The concentration of OTC in milk at 48 h was: IV= 0.6+/-0.4; IM CF= 1.1+/-0.2 and at 72 h (IM LA)= 0.6+/-0.1 microg/mL and the penetration in milk of OTC was: IV= 70.0+/-18.0; IM CF= 79.0+/-14.0 and IM LA= 66.0+/-6.0%. The areas under the curve of CK and LDH activities in plasma were calculated by the trapezoidal method. Values of CK and LDH IM, LA were greater (P < 0.05) than those observed for IM, CF at 2 and 3 days after administration of the antibiotic. Finally, the bioavailability of OTC CF = 92.0+/-22.0 and LA= 78.0+/-23.0% was suitable for its usage by the IM route in lactating goats. CONCLUSION: Plasma concentration-time values of OTC administered parenterally in production dairy goats showed similar bioavailability for the two pharmaceutical preaprations. The presence of detectable residues in milk indicates that milk should not be used for human consumption for 2 and 3 days after administration of conventional and long-acting formulations, respectively. The increments in CK and LDH activities after the IM administration of LA are consistent with the presence of tissue damage provoked by the pharmaceutical preparations at the injection site.     

Pharmacokinetics and intramuscular bioavailability of difloxacin in dromedary camels (Camelus dromedarius)

Single-dose disposition kinetics of difloxacin (5mg/kg bodyweight) were determined in clinically normal male dromedary camels (n=6) following intravenous (IV) and intramuscular (IM) administration. Difloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. The concentration-time data were analysed by compartmental and non-compartmental kinetic methods. Following a single IV injection, the plasma difloxacin concentration-time curve was best described by a two-compartment open model, with a distribution half-life (t(1/2alpha)) of 0.22+/-0.02h and an elimination half-life (t(1/2beta)) of 2.97+/-0.31h. Steady-state volume of distribution (V(dss)) and total body clearance (Cl(tot)) were 1.02+/-0.21L/kg and 0.24+/-0.07L/kg/h, respectively. Following IM administration, the absorption half-life (t(1)(/)(2ab)) and the mean absorption time (MAT) were 0.44+/-0.03h and 1.53+/-0.22h, respectively. The peak plasma concentration (C(max)) of 2.84+/-0.34microg/mL was achieved at 1.42+/-0.21h. The elimination half-life (t(1/2el)) and the mean residence time (MRT) was 3.46+/-0.42h and 5.61+/-0.23h, respectively. The in vitro plasma protein binding of difloxacin ranged from 28-43% and the absolute bioavailability following IM administration was 93.51+/-11.63%. Difloxacin could be useful for the treatment of bacterial infections in camels that are sensitive to this drug.     

Disposition kinetics of moxifloxacin in lactating ewes

The present study was planned to investigate the plasma disposition kinetics and the pattern of moxifloxacin elimination in the milk of lactating ewes (n=6) following a single intravenous (IV) bolus or intramuscular (IM) injections at a dosage of 5 mg/kg in all animals. A crossover study was carried out in two phases separated by 21 days. Plasma and milk samples were collected serially for 72 h and moxifloxacin concentrations were assayed using high performance liquid chromatography with fluorescence detection. A two-compartment open model best described the decrease of moxifloxacin concentration in the plasma after IV injection. The disposition after IM administration moxifloxacin was best described by a one-compartment model. Following IV administration, the distribution half-life (t(1/2alpha)) was 0.22+/-0.02 h. The elimination half-life was 1.77+/-0.23 h. The volume of distribution at steady state (V(dss)) was 0.84+/-0.12L/kg, the total body clearance (Cl(tot)) was 0.34+/-0.04 L/h/kg and the area under the curve (AUC) was 14.74+/-2.16 microg h/mL. Following IM administration, the mean T(max), C(max), t(1/2el) and AUC values for plasma data were 1.45+/-0.02 h, 2.21+/-0.27 microg/mL, 2.68+/-0.19 h and 14.21+/-2.35 microg h/mL. The IM bioavailability was 96.35+/-17.23% and the in vitro protein binding of moxifloxacin ranged from 32-37%. Penetration of moxifloxacin from the blood into milk was rapid and extensive, and the moxifloxacin concentrations in milk exceeded those in plasma from 1h after administration. The kinetic values AUC(milk)/AUC(plasma) and C(maxmilk)/C(maxplasma) ratios indicated a wide penetration of moxifloxacin from the bloodstream to the mammary gland. The in vitro minimum inhibitory concentration (MIC) of moxifloxacin for Mannheimia haemolytica was found to be 0.035 microg/mL.     

Pharmacokinetics and renal toxicity of three once-a-day doses of amikacin in cows

Pharmacokinetic variables of amikacin in cows were determined after administration of amikacin sulphate either intravenously (IV) or intramuscularly (IM) at a dose of 25 mg/kg per day for three days. Amikacin concentrations at time zero and maximum serum concentrations were 240.8 microg/mL and 122.53 microg/mL, respectively. The elimination half-life remained unchanged during the three days of administration (T1/2beta = 1.33 +/- 0.029 h for the IV route and T1/2beta = 2.75 +/- 0.38 h for the IM route). Apparent volumes of distribution suggest limited distribution out of the central compartment (VdAUC = 0.154 +/- 0.005 L/kg; Vdc = 36.50 +/- 2.35 L; Vdss = 0.092 +/- 0.004 L/kg). Bioavailability after IM administration was 95%. Serum profiles of urea, creatinine, albumin, electrolytes and pH after 5-day treatment with amikacin at a dose of 25 mg/kg per day IM revealed no changes. Assessment of diffusion of amikacin to milk by a commercially available screening method to detect antibiotic residues revealed that amikacin could not be detected by the fifth milking period after the last treatment. These results suggest that it would be rational to use a large single-daily dose of amikacin for future clinical trials in cows.     

Pharmacokinetic behaviour of enrofloxacin in greater rheas following a single-dose intramuscular administration

The pharmacokinetic behaviour of enrofloxacin in greater rheas was investigated after intramuscular (IM) administration of 15 mg/kg. Plasma concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were determined by high performance liquid chromatography. Enrofloxacin peak plasma concentration (C(max)=3.30+/-0.90 microg/mL) was reached at 24.17+/-9.17 min. The terminal half-life (t(1/2lambda)) and area under the curve (AUC) were 2.85+/-0.54 h and 4.18+/-0.69 microg h/mL, respectively. The AUC and C(max) for ciprofloxacin were 0.25+/-0.06 microg/mL and 0.66+/-0.16 microg h/mL, respectively. Taking into account the values obtained for the efficacy indices, an IM dose of 15 mg/kg of enrofloxacin would appear to be adequate for treating infections caused by highly susceptible bacteria (MIC(90)<0.03 microg/mL) in greater rheas.     

Evaluation of bioequivalence after oral, intramuscular, and intravenous administration of racemic ketoprofen in pigs

OBJECTIVE: To assess bioequivalence after oral, IM, and IV administration of racemic ketoprofen in pigs and to investigate the bioavailability after oral and IM administration. ANIMALS: 8 crossbred pigs. PROCEDURES: Each pig received 4 treatments in a randomized crossover design, with a 6-day washout period. Ketoprofen was administered at 3 and 6 mg/kg, PO; 3 mg/kg, IM; and 3 mg/kg, IV. Plasma ketoprofen concentrations were measured by use of high-performance liquid chromatography for up to 48 hours. To assess bioequivalence, a 90% confidence interval was calculated for the area under the time-concentration curve (AUC) and maximum plasma concentration (C(max)). RESULTS: Equivalence was not detected in the AUCs among the various routes of administration nor in C(max) between oral and IM administration of 3 mg/kg. The bioavailability of ketoprofen was almost complete after each oral or IM administration. Mean +/- SD C(max) was 5.09 +/- 1.41 microg/mL and 7.62 +/- 1.22 microg/mL after oral and IM doses of 3 mg/kg, respectively. Mean elimination half-life varied from 3.52 +/- 0.90 hours after oral administration of 3 mg/kg to 2.66 +/- 0.50 hours after IV administration. Time to peak C(max) after administration of all treatments was approximately 1 hour. Increases in AUC and C(max) were proportional when the orally administered dose was increased from 3 to 6 mg/kg. Conclusions and Clinical Relevance: Orally administered ketoprofen was absorbed well in pigs, although bioequivalence with IM administration of ketoprofen was not detected. Orally administered ketoprofen may have potential for use in treating pigs.     

Pharmacokinetics of a combination preparation of ampicillin and sulbactam in turkeys

OBJECTIVE: To investigate the disposition kinetics of ampicillin and sulbactam after IV and IM administration of an ampicillin-sulbactam (2:1) preparation and determine the bioavailability of the combined preparation after IM administration in turkeys. ANIMALS: 10 healthy large white turkeys. PROCEDURE: In a crossover study, turkeys were administered the combined preparation IV (20 mg/kg) and IM (30 mg/kg). Blood samples were collected before and at intervals after drug administrations. Plasma ampicillin and sulbactam concentrations were measured by use of high-performance liquid chromatography; plasma concentration-time curves were analyzed via compartmental pharmacokinetics and noncompartmental methods. RESULTS: The drugs were distributed according to an open 2-compartment model after IV administration and a 1-compartment model (first-order absorption) after IM administration. For ampicillin and sulbactam, the apparent volumes of distribution were 0.75+/-0.11 L/kg and 0.74+/-0.10 L/kg, respectively, and the total body clearances were 0.67+/-0.07 L x kg(-1) x h(-1) and 0.56+/-0.06 L x kg(-1) x h(-), respectively. The elimination half-lives of ampicillin after IV and IM administration were 0.78+/-0.12 hours and 0.89+/-0.17 hours, respectively, whereas the corresponding half-lives of sulbactam were 0.91+/-0.12 hours and 0.99+/-0.16 hours, respectively. Bioavailability after IM injection was 58.87+/-765% for ampicillin and 53.75+/-5.35% for sulbactam. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that a regimen of loading and maintenance doses of 300 mg of the ampicillin-sulbactam (2:1) combination/kg every 8 hours could be clinically useful in turkeys. This dosage regimen maintained plasma concentrations of ampicillin > 0.45 microg/mL in turkeys.     

The pharmacokinetics, metabolism and urinary detection time of tramadol in camels

The pharmacokinetics of tramadol in camels (Camelus dromedarius) were studied following a single intravenous (IV) and a single intramuscular (IM) dose of 2.33 mg kg(-1) bodyweight. The drug's metabolism and urinary detection time were also investigated. Following both IV and IM administration, tramadol was extracted from plasma using an automated solid phase extraction method and the concentration measured by gas chromatography-mass spectrometry (GC/MS). The plasma drug concentrations after IV administration were best fitted by an open two-compartment model. However a three-compartment open model best fitted the IM data. The results (means+/-SEM) were as follows: after IV drug administration, the distribution half-life (t(1/2)(alpha)) was 0.22+/-0.05 h, the elimination half-life (t(1/2)(beta)) 1.33+/-0.18 h, the total body clearance (Cl(T)) 1.94+/-0.18 L h kg(-1), the volume of distribution at steady state (Vd(ss)) 2.58+/-0.44 L kg(-1), and the area under the concentration vs. time curve (AUC(0-infinity)) 1.25+/-0.13 mg h L(-1). Following IM administration, the maximal plasma tramadol concentration (C(max)) reached was 0.44+/-0.07 microg mL(-1) at time (T(max)) 0.57+/-0.11h; the absorption half-life (t(1/2 ka)) was 0.17+/-0.03 h, the (t(1/2)(beta)) was 3.24+/-0.55 h, the (AUC(0-infinity)) was 1.27+/-0.12 mg h L(-1), the (Vd(area)) was 8.94+/-1.41 L kg(-1), and the mean systemic bioavailability (F) was 101.62%. Three main tramadol metabolites were detected in urine. These were O-desmethyltramadol, N,O-desmethyltramadol and/or N-bis-desmethyltramadol, and hydroxy-tramadol. O-Desmethyltramadol was found to be the main metabolite. The urinary detection times for tramadol and O-desmethyltramadol were 24 and 48 h, respectively. The pharmacokinetics of tramadol in camels was characterised by a fast clearance, large volume of distribution and brief half-life, which resulted in a short detection time. O-Desmethyltramadol detection in positive cases would increase the reliability of reporting tramadol abuse.     

Intraocular pharmacokinetics of intravenously administered marbofloxacin in rabbits with experimentally induced acute endophthalmitis

OBJECTIVE: To compare penetration of IV administered marbofloxacin in intraocular fluids of healthy and inflamed eyes in rabbits with endotoxin-induced endophthalmitis. ANIMALS: 35 pigmented rabbits. PROCEDURES: Endophthalmitis was induced in the right eye via intravitreal administration of Escherichia coli endotoxin. The left eye was a control eye. After 24 hours, a single dose of marbofloxacin (4 mg/kg, IV) was administered. Groups of rabbits (n = 5/group) were euthanized 0.5, 1, 2, 4, 6, 10, and 18 hours later, and blood and ocular fluids were collected. Marbofloxacin concentrations were determined via reverse-phase high-performance liquid chromatography, and pharmacokinetic analysis of the data was performed with a mono-compartmental model. RESULTS: Mean area under the aqueous concentration-time curve was significantly lower in control eyes (1.64 +/- 0.07 microg*h/mL) than in inflamed eyes (3.31 +/- 0.11 microg*h/mL). Similarly, drug penetration into aqueous humor was 33% and 65% for control eyes and inflamed eyes, respectively. Mean area under the vitreous humor concentration-time curve for control eyes(1.75 +/- 0.05 microg*h/mL) was significantly less than for inflamed eyes (2.39 +/- 0.16 microg*h/mL). In the vitreous humor, corresponding penetrations were 34% and 47%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Penetration of marbofloxacin into the aqueous and vitreous humor after IV administration was significantly enhanced by intraocular inflammation, suggesting a role for this antimicrobial in the prophylaxis or treatment of bacterial endophthalmitis caused by susceptible pathogens.     

Disposition kinetics and pharmacokinetics--pharmacodynamic integration of difloxacin against Staphylococcus aureus isolates from rabbits

The pharmacokinetics of difloxacin were studied following intravenous (IV), subcutaneous (SC) and oral administration of 5mg/kg to healthy white New Zealand rabbits (n = 6). Difloxacin concentrations were determined by HPLC assay with fluorescence detection. Minimal inhibitory concentrations (MICs) assay of difloxacin against different strains of S. aureus from different european countries was performed in order to compute the main pharmacodynamic surrogate markers. The plasma difloxacin clearance (Cl) for the IV route was (mean +/- SD) 0.41 +/- 0.05 L/h kg. The steady-state volume of distribution (V(ss)) was 1.95 +/- 0.17 L/kg. The terminal half-life [Formula: see text] was (mean+/-SD) 4.19+/-0.34 h, 7.53 +/- 1.32 h and 8.00 +/- 0.45 h after IV, IM and oral, respectively. From this data, it seems that a 5 mg/kg dose difloxacin would be effective by SC and oral routes in rabbits against bacterial isolates with MIC0.1 microg/mL.     

Pharmacokinetics after intravenous, intramuscular and subcutaneous administration of difloxacin in sheep

The disposition kinetics of difloxacin, a fluoroquinolone antibiotic, after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration were determined in sheep at a single dose of 5mg/kg. The concentration-time data were analysed by compartmental (after IV dose) and non-compartmental pharmacokinetics method (after IV, IM and SC administration). Plasma concentrations of difloxacin were determined by high performance liquid chromatography with fluorescence detection. Steady-state volume of distribution (V(ss)) and clearance (Cl) of difloxacin after IV administration were 1.68+/-0.21L/kg and 0.21+/-0.03L/hkg, respectively. Following IM and SC administration difloxacin achieved maximum plasma concentration of 1.89+/-0.55 and 1.39+/-0.14mg/L at 2.42+/-1.28 and 5.33+/-1.03h, respectively. The absolute bioavailabilities after IM and SC routes were 99.92+/-26.50 and 82.35+/-25.65%, respectively. Based on these kinetic parameters, difloxacin is likely to be effective in sheep.     

Enrofloxacin and marbofloxacin in horses: comparison of pharmacokinetic parameters, use of urinary and metabolite data to estimate first-pass effect and absorbed fraction

Enrofloxacin and marbofloxacin are two veterinary fluoroquinolones used to treat severe bacterial infections in horses. A repeated measures study has been designed to compare their pharmacokinetic parameters, to investigate their bioavailability and to estimate their absorbed fraction and first-pass effect by using plasma, urinary and metabolite data collected from five healthy mares. Clearance and V(d(ss)) were greater for enrofloxacin (mean +/- SD = 6.34 +/- 1.5 mL/min/kg and 2.32 +/- 0.32 L/kg, respectively) than for marbofloxacin (4.62 +/- 0.67 mL/min/kg and 1.6 +/- 0.25 L/kg, respectively). Variance of the AUC(0-inf) of marbofloxacin was lower than that for enrofloxacin, with, respectively, a CV = 15% and 26% intravenously and a CV = 31% and 55% after oral administration. Mean oral bioavailability was not significantly different between marbofloxacin (59%) and enrofloxacin (55%). The mean percentage of the dose eliminated unchanged in urine was significantly higher for marbofloxacin (39.7%) than that for enrofloxacin (3.4%). Absorbed fraction and first-pass effect were only determinable for enrofloxacin, whereas the percentage of the dose absorbed in the portal circulation was estimated to be 78% and the fraction not extracted during the first pass through the liver was 65%. Consequently, the moderate observed bioavailability of enrofloxacin appears to be mainly caused by hepatic first-pass effect.     

Pharmacokinetics of disodium-fosfomycin in mongrel dogs

Pharmacokinetic variables of fosfomycin were determined after administration of buffered disodium-fosfomycin intravenously (IV), intramuscularly (IM), subcutaneously (SC) and orally (PO), in mongrel dogs, at 40 and 80 mg/kgday for three days. Renal integrity was also assessed by measuring key serum variables. Day 1, day 2 and day 3 plasma concentration vs. time profiles were undistinguishable, but there appears to be a lineal increase in serum concentrations vs. time with the dose. A non-accumulative kinetic behavior was observed after three days with both doses and most pharmacokinetic variables remain unaltered. Considering a MIC range from 1 mirog/mL to 16 microg/mL of fosfomycin in serum for sensitive bacteria, and a negligible plasma protein binding of fosfomycin (<0.5%), useful plasma concentrations can only be achieved after the SC injection of 80 mg/kg every 12h, having a C(max)=18.96+/-0.3 microg/mL; a T(1/2beta)=2.09+/-0.06 microg/mL and a bioavailability of 84-85%. No alterations were observed in serum variables of kidney-related biochemical values.     

Pharmacokinetics and bioavailability of ceftriaxone administered intravenously and intramuscularly to calves

Ceftriaxone was administered to Israeli-Friesian male calves by IV and IM routes. The antibiotic was administered IV (10 mg/kg) to 10 calves and IM to 23 calves; 8 were given the antibiotic at the rate of 10 mg/kg of body weight, 5 were given 20 mg/kg, and 10 were given 10 mg/kg, together with probenecid at 40 mg/kg. Serum concentration vs time profiles measured after IV and IM administration were analyzed by use of statistical moment theory. The following mean values +/- SD were found: elimination half-life (t1/2) was 83.8 +/- 8.6 minutes after IV administration and significantly longer 116.8 +/- 20.5 minutes (P less than 0.001) after IM administration at 10 mg/kg. The t1/2 was increased to 141.3 +/- 24.4 minutes by the coadministration of probenecid and to 145.0 +/- 48.2 minutes by doubling the IM dosage to 20 mg/kg. The total body clearance was 3.39 +/- 0.42 ml/min/kg and the renal clearance 2.37 +/- 0.74 ml/min/kg. The specific volume of distribution was 0.2990 +/- 0.0510 L/kg. The average mean residence time (MRT) was 94.0 +/- 12.3 minutes after IV administration and 137.6 +/- 19.9 minutes after IM administration of ceftriaxone at 10 mg/kg. The MRT was increased to 198 +/- 48.8 minutes by the coadministration of probenecid and to 191.0 +/- 59.4 minutes by doubling the IM dose. The former value was significantly different from the MRT after IM administration of the antibiotic at 10 mg/kg. Bioavailability of ceftriaxone after IM administration at 10 mg/kg and at 20 mg/kg was 78% and 83%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of difloxacin after intravenous, intramuscular, and intragastric administration to horses

OBJECTIVE: To study the pharmacokinetics of difloxacin (5 mg/kg) following IV, IM, and intragastric (IG) administration to healthy horses. ANIMALS: 6 healthy mature horses. PROCEDURES: A crossover study design with 3 phases was used (15-day washout periods between treatments). An injectable formulation of difloxacin (5%) was administered IV and IM in single doses (5 mg/kg); for IG administration, an oral solution was prepared and administered via nasogastric tube. Blood samples were collected before and at intervals after each administration. A high-performance liquid chromatography assay with fluorescence detection was used to determine plasma difloxacin concentrations. Pharmacokinetic parameters of difloxacin were analyzed. Plasma creatine kinase activity was monitored to assess tissue damage. RESULTS: Difloxacin plasma concentration versus time data after IV administration were best described by a 2-compartment open model. The disposition of difloxacin following IM or IG administration was best described by a 1-compartment model. Mean half-life for difloxacin administered IV, IM, and IG was 2.66, 5.72, and 10.75 hours, respectively. Clearance after IV administration was 0.28 L/kg.h. After IM administration, the absolute mean +/- SD bioavailability was 95.81 +/- 3.11% and maximum plasma concentration (Cmax) was 1.48 +/- 0.12 mg/L. After IG administration, the absolute bioavailability was 68.62 +/- 10.60% and Cmax was 0.732 +/- 0.05 mg/L. At 12 hours after IM administration, plasma creatine kinase activity had increased 7-fold, compared with the preinjection value. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggest that difloxacin is likely to be effective for treating susceptible bacterial infections in horses.