Pharmacokinetics and body fluid and endometrial concentrations of cefoxitin in mares

Four healthy adult mares were each given a single injection of sodium cefoxitin (20 mg/kg of body weight, IV), and serum cefoxitin concentrations were measured serially during a 6-hour period. The mean elimination rate constant was 1.08/hour and the elimination half-life was 0.82 hour. The apparent volume of distribution (at steady state) and the clearance of the drug were estimated at 0.12 L/kg and 259 ml/hr/kg, respectively. Each mare and 2 additional mares were then given 4 consecutive IM injections of sodium cefoxitin (400 mg/ml) at a dosage of 20 mg/kg. Cefoxitin concentrations in serum, synovial fluid, peritoneal fluid, CSF, urine, and endometrium were measured serially. After IM administration, the highest mean serum concentration was 23.1 micrograms/ml 30 minutes after the 2nd injection. The highest mean synovial concentration was 11.4 micrograms/ml 1 hour after the 4th injection. The highest mean peritoneal concentration was 10.4 micrograms/ml 2 hours after the 4th injection. The highest mean endometrial concentration was 4.5 micrograms/g 4 hours after the 4th injection. Mean urine concentrations reached 11,645 micrograms/ml. Cefoxitin did not readily penetrate the CSF. Bioavailability of cefoxitin given IM was 65% to 89% (mean +/- SEM = 77% +/- 5.9%). One of the 6 mares developed acute laminitis during the IM experiment.     

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.     

Pharmacokinetics of phenobarbital in the horse

Pharmacokinetics of phenobarbital was examined in 6 mature horses after 12 mg of phenobarbital/kg of body weight was infused over 20 minutes. Biexponential decrease in serum phenobarbital concentrations was observed with a distribution-phase half-life of 0.101 +/- 0.086 hour (mean +/- SD) and a terminal-phase elimination half-life of 18.3 +/- 3.65 hours. The volume of distribution at steady state was 0.803 +/- 0.070 L/kg. Total body clearance of phenobarbital was 30.8 +/- 6.2 ml/h/kg. The high clearance in the horse seems to explain the markedly shorter half-life of phenobarbital in this species. Seemingly, 6.65 mg of phenobarbital/kg as a 20-minute infusion given every 12 hours would provide approximate peaks of 29 micrograms/ml and troughs of 15 micrograms/ml. A loading dose of 12 mg of phenobarbital/kg would be appropriate for this regimen.     

Pharmacokinetics and renal clearance of ampicillin in sheep

Pharmacokinetics and renal clearance of ampicillin were investigated in 13 sheep, following one single oral dose of 750 mg. A peak concentration in plasma 0.38 +/- 0.04 microgram/ml (mean +/- SEM) was achieved 95.3 +/- 5.95 min after drug administration. Absorption half-life was 44.4 +/- 4.4 min. The area under the plasma concentration curve was 94.6 +/- 4.5 micrograms.hour.ml-1, while in the case of urine it was 370.5 +/- 28.3 micrograms.hour.ml-1. Biological half-life of ampicillin was 110 +/- 3 min, with an elimination rate constant of 0.0064 +/- 0.0002 min-1. The values for volume of distribution and total body clearance were 8.2 +/- 0.71/kg or 52.0 +/- 4.2 ml/kg/min, respectively. The priming and maintenance doses, using MIC as 0.05 microgram/ml, were suggested to be 8.8 or 8.4 mg/kg, respectively, at an 8-h interval. For MIC of 0.5 microgram/ml, this dose should be 10 times higher. Renal clearance of ampicillin seemed to involve active tubular secretion. Renal excretion indicated either extensive metabolism or excretion through routes other than kidneys.     

Pharmacokinetics, bioavailability, and in vitro antibacterial activity of rifampin in the horse

The pharmacokinetics and bioavailability of rifampin were determined after IV (10 mg/kg of body weight) and intragastric (20 mg/kg of body weight) administration to 6 healthy, adult horses. After IV administration, the disposition kinetics of rifampin were best described by a 2-compartment open model. A rapid distribution phase was followed by a slower elimination phase, with a half-life (t1/2[beta]) of 7.27 +/- 1.11 hours. The mean body clearance was 1.49 +/- 0.41 ml/min.kg, and the mean volume of distribution was 932 +/- 292 ml/kg, indicating that rifampin was widely distributed in the body. After intragastric administration of rifampin in aqueous suspension, a brief lag period (0.31 +/- 0.09 hour) was followed by rapid, but incomplete, absorption (t1/2[a] = 0.51 +/- 0.32 hour) and slow elimination (t1/2[d] = 11.50 +/- 1.55 hours). The mean bioavailability (fractional absorption) of the administered dose during the first 24 hours was 53.94 +/- 18.90%, and we estimated that 70.0 +/- 23.6% of the drug would eventually be absorbed. The mean peak plasma rifampin concentration was 13.25 +/- 2.70 micrograms/ml at 2.5 +/- 1.6 hours after dosing. All 6 horses had plasma rifampin concentrations greater than 2 micrograms/ml by 45 minutes after dosing; concentrations greater than 3 micrograms/ml persisted for at least 24 hours. Mean plasma rifampin concentrations at 12 and 24 hours after dosing were 6.86 +/- 1.69 micrograms/ml and 3.83 +/- 0.87 micrograms/ml, respectively. We tested 162 isolates of 16 bacterial species cultured from clinically ill horses for susceptibility to rifampin.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Lack of gender effect on the pharmacokinetics and pharmacodynamics of dexamethasone in the camel after intravenous administration

The pharmacokinetics and pharmacodynamics of dexamethasone were studied in six male and six female camels after a single intravenous dose (0.05 mgkg(-1) body weight) of dexamethasone. The pharmacokinetic parameters of the two-compartment pharmacokinetic model for female and male camels, respectively (mean+/-SEM) were as follows: terminal elimination half-lives were 8.02+/-1.15 and 7.33+/-0.80 h, total body clearances were 95.5+/-16.0 and 124.5+/-11.9 ml h(-1) per kg, volumes of distribution at steady state were 0.72+/-0.08 and 0.87+/-0.14 litre kg(-1), and the volumes of the central compartment were 0.12+/-0.02 and 0.17+/-0.02 litre kg(-1). There was no significant difference in any pharmacokinetic parameter between female and male camels. Pharmacodynamic effects were evaluated by measuring endogenous plasma cortisol, circulating lymphocytes and neutrophils numbers and were analysed using indirect pharmacokinetic/pharmacodynamic models. The estimated IC50 of dexamethasone for cortisol and lymphocytes for female and male camels were 3.74+/-0.99 and 2.28+/-1.09 and 2.63+/-0.71 and 2.41+/-0.79 ng ml(-1), respectively. The EC50 for neutrophils for female and male camels were 24.5+/-5.83 and 20.2+/-3.82 ng ml(-1), respectively. There was no significant difference in any pharmacodynamic parameter between female and male camels. Dexamethasone in urine could be detected for 4-5 days by enzyme-linked immunosorbent assay and for 3-4 days by liquid chromatography/mass spectrometry after an intravenous dose of 0.05 mg kg(-1) body weight.     

Comparative pharmacokinetics of theophylline in camels (Camelus dromedarius) and goats (Caprus hircus)

A comparative randomized crossover study was conducted to determine the pharmacokinetics of theophylline in male and female camels (Camelus dromedarius) and goats (Caprus hircus). Theophylline is an established 'probe drug' to evaluate the drug metabolizing enzyme activity of animals. It was administered by the intravenous (i.v.) route and then intramuscularly (i.m.) at a dose of 2 mg/kg. The concentration of the drug in plasma was measured using a high-performance liquid chromatography (HPLC) technique on samples collected at frequent intervals after administration. Following i.v. injection, the overall elimination rate constant (lambda z,) in goats was 0.006 +/- 0.00076/min and in camels was 0.0046 +/- 0.0008/min (P < 0.01). The elimination half-life (t 1/2 lambda z) in goats (112 .7 min) was lower than in camels (154.7 min) (P < 0.01). The apparent volume of distribution (Vz) and the total body clearance (Cl) in goats were 1440.1 +/- 166.6 ml/kg and 8.9 +/- 1.4 ml/min/kg, respectively. The corresponding values in camels were 1720.3 +/- 345.3 ml/kg and 6.1 +/- 1.0 ml/min/kg, respectively. After i.m. administration, theophylline reached a peak plasma concentration (Cmax) of 1.8 +/- 0.1 and 1.7 +/- 0.2 microg/ml at a post-injection time (Tmax) of 67.5 +/- 8.6 and 122.3 +/- 6.7 min in goats and camels, respectively. The mean bioavailability (T) in both goats and camels was 0.9 +/- 0.2. The above data suggest that camels eliminate theophylline at a slower rate than goats.     

The disposition of diclofenac in camels after intravenous administration

The pharmacokinetics of diclofenac was studied in camels (Camelus dromedarus) (n=6) following intravenous (i.v.) administration of a dose of 2.5 mg kg(-1) body weight. The metabolism and urinary detection time were also studied. The results obtained (median and range) were as follows: the terminal elimination half-life (t(1/2beta)) was 2.35 (1.90-2.73)h, total body clearance (Cl(T)) was 0.17 (0.16-0.21)lh kg(-1). The volume of distribution at steady state (V(SS)) was 0.31 (0.21-0.39)l(-1)kg(-1), the volume of the central compartment of the two compartment pharmacokinetic model (V(C)) was 0.15 (0.11-0.17)l kg(-1). Five metabolites of diclofenac were tentatively identified in urine and were excreted mainly in conjugate form. The main metabolite was identified as hydroxy diclofenac. Both diclofenac and hydroxy diclofenac, appear to be the main elimination route for diclofenac when administered i.v. in camels. Diclofenac could be identified up to 4 days following i.v. administration in camels using a sensitive gas chromatography/mass spectrometry (GC/MS) method.     

Pharmacokinetics and Dosage Regimen of Ceftriaxone in Buffalo Calves

The pharmacokinetics and dosage regimen of ceftriaxone were investigated in buffalo calves (n = 6) following a single intravenous administration of ceftriaxone (10 mg/kg). The elimination rate constant was 0.18 +/- 0.01 h(-1) and the elimination half-life was 3.79 +/- 0.09 h. The apparent volume of distribution (Vd(area)) was 1.40 +/- 0.01 L/kg and the total plasma clearance was 0.26 +/- 0.01 L/(kg h). Approximately 43% of total administered dose of ceftriaxone was excreted in urine within 8 h. To maintain a minimum therapeutic concentration of 1 microg/ml, a satisfactory intravenous dosage regimen of ceftriaxone in buffalo calves is 13 mg/kg repeated at 12 h intervals.     

Pharmacokinetics and bioavailability of spiramycin in pigs.

The pharmacokinetics of spiramycin in pigs were investigated after intravenous and oral administration. The potential therapeutically effective blood level was established after a single administration and examined in a subsidiary five day study. The rapid intravenous injection of 25 mg spiramycin/kg bodyweight produced marked salivation in all the test animals. The elimination half-life (2.3 +/- 1.2 hours) was relatively short, in accordance with the total body clearance rate (27.3 +/- 10.1 ml/minute/kg). The high volume of distribution (5.2 +/- 2.2 litres/kg) was due to the accumulation of the drug in the body tissues. The maximum plasma concentration (4.1 +/- 1.7 micrograms/ml) after oral administration of 85 to 100 mg spiramycin/kg bodyweight was reached after 3.7 +/- 0.8 hours and the half-life of the elimination phase was 6.0 +/- 2.4 hours. The oral bioavailability was 45.4 +/- 23.4 per cent. Ad libitum feeding of a diet containing 2550 mg spiramycin/kg produced a steady state concentration of 0.96 +/- 0.27 micrograms/ml. This plasma concentration would provide a potentially therapeutically effective blood concentration against Mycoplasma species, Streptococcus species and Staphylococcus species.     

Pharmacokinetics and pharmacodynamics of piroxicam in dogs

Piroxicam was administered to beagle dogs intravenously and orally at a dose rate of 0.3 mg/kg bodyweight. It had an elimination half-life of 40.2 hours, a volume of distribution of 0.29 +/- 0.02 litres/kg and a body clearance rate of 0.066 litres/hour. When administered orally it was 100 per cent bioavailable and maximum plasma concentrations were achieved quickly (3.1 +/- 1.0 hours). Piroxicam inhibited the generation of thromboxane B2 in the blood of dogs by more than 70 per cent and more than 50 per cent inhibition was maintained in most animals for 48 hours.     

Disposition Kinetics,Bioavailability and Renal Clearance of Cefepime in Calves

The pharmacokinetics of cefepime were studied following intravenous and intramuscular administration of 6.5 mg/kg in four female Friesian calves. Following single intravenous administration, the serum concentration-time curves of cefepime were best fitted using a two-compartment open model. The elimination half-life (t(1/2)beta) was 2.38+/-0.16 h, volume of distribution at steady state (Vdss) was 0.21 +/- 0.01 L/kg, and total body clearance (ClB) was 1.1 +/- 0.08 ml/min per kg. Following intramuscular administration, the drug was rapidly absorbed with an absorption half-life (t(1/2)ab) of 0.29+/-0.02 h; maximum serum concentration (Cmax) of 21.7 +/- 1.1 microg/ml was attained after (Tmax) 1.1 +/- 0.08 h; and the drug was eliminated with an elimination half-life (t(1/2)el) of 3.02 +/- 0.18 h. The systemic bioavailability (F) after intramuscular administration of cefepime in calves was 95.7% +/- 7.44%. The in vitro serum protein-binding tendency was 10.5-16.7%. Following administration by both routes, the drug was excreted in high concentrations in urine for 24 h post administration.     

Pharmacokinetics of single-dose intravenous or intramuscular administration of gentamicin in roosters

Healthy mature roosters (n = 10) were given gentamicin (5 mg/kg of body weight, IV) and, 30 days later, another dose IM. Serum concentrations of gentamicin were determined over 60 hours after each drug dosing, using a radioimmunoassay. Using nonlinear least-square regression methods, the combined data of IV and IM treatments were best fitted by a 2-compartment open model. The mean distribution phase half-life was 0.203 +/- 0.075 hours (mean +/- SD) and the terminal half-life was 3.38 +/- 0.62 hours. The volume of the central compartment was 0.0993 +/- 0.0097 L/kg, volume of distribution at steady state was 0.209 +/- 0.013 L/kg, and the total body clearance was 46.5 +/- 7.9 ml/h/kg. Intramuscular absorption was rapid, with a half-life for absorption of 0.281 +/- 0.081 hours. The extent of IM absorption was 95 +/- 18%. Maximal serum concentration of 20.68 +/- 2.10 micrograms/ml was detected at 0.62 +/- 0.18 hours after the dose. Kinetic calculations predicted that IM injection of gentamicin at a dosage of 4 mg/kg, q 12 h, and 1.5 mg/kg, q 8 h, would provide average steady-state serum concentrations of 6.82 and 3.83 micrograms/ml, with minimal steady-state serum concentrations of 1.54 and 1.50 micrograms/ml and maximal steady-state serum concentrations of 18.34 and 7.70 micrograms/ml, respectively.     

Pharmacokinetics and metabolic inertness of doxycycline in young pigs

The disposition of doxycycline hyclate after IV administration of 20 mg/kg of body weight was studied in 6 pigs. Median elimination half-life, estimated in 4 pigs, was 3.92 hours. Mean (+/- SEM) total body clearance was 1.67 +/- 0.18 ml/min/kg, and mean apparent volume of distribution at steady state was 0.53 +/- 0.04 L/kg. In 2 pigs, secondary peaks in the logarithmic serum concentration-time profile suggested discontinuous enterohepatic cycling, and precluded using these pigs in the pharmacokinetic analysis. The extent of doxycycline binding to serum protein was 93.1 +/- 0.2%. Serum or urine from 3 of the pigs was analyzed by use of photodiode array detection and mass spectrometry of a high-performance liquid chromatographic column effluent. These procedures documented lack of doxycycline biotransformation in pigs. It is concluded that, despite an elimination half-life shorter than that reported in other species, doxycycline may be a valuable antimicrobial drug for use in swine practice, pending the development of appropriate formulations.     

Pharmacokinetic parameters of ceftriaxone after single intravenous and intramuscular administration in camels (Camelus Dromedarius)

The purpose of this study was to investigate the plasma disposition kinetics of ceftriaxone in female camels (n=5) following a single intravenous (i.v.) bolus or intramuscular (i.m.) injections at a dosage of 10mg kg(-1) body weight in all animals. A crossover design was carried out in two phases separated by 15 days. Jugular blood samples were collected serially for 48h and the plasma was analysed by high-performance liquid chromatography (HPLC). Following single i.v. injections the plasma concentration time curves of ceftriaxone were best fitted to a two-compartment model. The drug was rapidly distributed with half-life of distribution t(1/2alpha) of 0.24+/-0.01h and moderately eliminated with elimination rate constant and elimination half-life of 0.27+/-0.13h(-1) and 2.57+/-0.52h, respectively. The volume of distribution at steady state (V(dss)) was 0.32+/-0.01lkg(-1) and the total body clearance (Cl(tot)) was 0.11+/-0.01lkg(-1)h(-1), respectively. Following i.m. administration, the mean T(max), C(max), t(1/2el) and AUC values for plasma data were 1.03+/-0.23h, 21.54+/-2.61microg ml(-1), 1.76+/-0.03h and 85.82+/-11.21microg ml(-1)h(-1), respectively. The i.m. bioavailability was 93.42+/-21.4% and the binding percentage of ceftriaxone to plasma protein was moderate, ranging from 33% to 42% with an average of 34.5%.     

Effect of probenecid on disposition kinetics of ampicillin in horses.

The effect of an oral dose of probenecid on the disposition kinetics of ampicillin was determined in four horses. An intravenous bolus dose (10 mg/kg) of ampicillin sodium was administered to the horses on two occasions. On the first occasion the antibiotic was administered on its own, and on the second occasion it was administered one hour after an oral dose of 75 mg/kg probenecid. The plasma concentration of probenecid reached a mean (+/- se) maximum concentration (Cmax) of 188-6 +/- 19.3 micrograms/ml after 120.0 +/- 21.2 minutes and concentrations greater than 15 micrograms/ml were present 25 hours after it was administered. The disposition kinetics of ampicillin were altered by the presence of probenecid and as a result the antibiotic had a slower body clearance (ClB; 109.4 +/- 6.71 ml/kg hours compared with 208.9 +/- 26.2 ml/kg hours) a longer elimination half-life (t1/2 beta 1.198 hours compared with 0.701 hours) and consequently a larger area under the plasma concentration versus time curve (AUC 92.3 +/- 5.09 mg/ml hours compared with 35.95 +/- 3.45 mg/ml hours) when compared with animals to which ampicillin was administered alone. The ampicillin concentrations observed suggest that the dosing interval for horses may be increased from between six and eight hours to 12 hours when probenecid is administered in conjunction with the ampicillin.     

Pharmacokinetics of sodium amoxicillin in foals after intramuscular administration

Pharmacokinetic values of sodium amoxicillin (22 mg/kg of body weight) in foals were determined after a single IM injection in 6 Quarter Horse foals at 3, 10, and 30 days of age. Serum amoxicillin concentrations were measured serially over a 24-hour period. The absorption of amoxicillin was rapid and followed a 1st-order elimination. Mean peak serum concentrations occurred 30 minutes after the injection in foals at all ages and were 17.31 +/- 9.59 micrograms/ml when the foals were 3 days old, 23.28 +/- 9.86 micrograms/ml when the foals were 10 days old, and 21.35 +/- 6.39 micrograms/ml when the foals were 30 days old. Serum samples collected beyond 8 hours after administration contained amoxicillin concentrations less than 0.05 micrograms/ml. The elimination rate constant increased with increasing age (0.5265 +/- 0.0891 hour-1 when the foals were 3 days old, 0.6494 +/- 0.1114 hour-1 when the foals were 10 days old, and 0.7112 +/- 0.1016 hour-1 when the foals were 30 days old). Serum clearance increased with increasing age (498.4 +/- 82.6 ml/hr/kg at 3 days, 631.6 +/- 170.5 ml/hr/kg at 10 days, and 691.2 +/- 127.3 ml/hr/kg at 30 days). Serum half-life decreased with increasing age (1.34 +/-0.243 hour at 3 days, 1.10 +/- 0.239 hour at 10 days, and 0.991 +/- 0.139 hour at 30 days), whereas the extrapolated concentration at time zero and apparent volume of distribution did not change during the first 30 days of age.     

Pharmacokinetics of ticarcillin in the dog

Five healthy adult dogs were given a single IV dose (40 mg/kg of body weight) of ticarcillin disodium. Serum concentrations were measured serially over a period of 12 hours. Five days later, the drug was administered IM to the dogs at the same dose rate, and serum concentrations were measured serially for 12 hours. The mean peak serum concentration after IM administration was 120.5 micrograms/ml at 1.5 hours. Pharmacokinetic values following IV administration were (i) elimination rate constant = 0.8/hour-1, (ii) half-life = 0.8 hour, (iii) serum clearance = 292 ml/hr/kg, and (iv) apparent volume of distribution = 347 ml/kg. Estimated values after IM administration were (i) elimination rate constant = 0.6/hour, (ii) half-life = 1.1 hours, (iii) serum clearance = 218 ml/hr/kg, and (iv) apparent volume of distribution = 345 ml/kg; only the elimination rate constants were significantly different between the 2 routes of administration.     

Pharmacokinetics of cefepime administered by i.v. and i.m. routes to ewes

The pharmacokinetics of cefepime were studied following i.v. and i.m. administration of 20 mg/kg in 10 ewes. Following i.v. administration of a single dose, the plasma concentration-time curves of cefepime were best fitted using a two-compartment open model. The elimination half-life (t(1/2beta)) was 1.76 +/- 0.07 h, volume of distribution at steady-state [V(d(ss))] was 0.32 +/- 0.01 L/kg and total body clearance (Cl(B)) was 2.37 +/- 0.05 mL/min.kg. Following i.m. administration, the drug was rapidly absorbed with an absorption half-life (t(1/2ab)) of 0.49 +/- 0.05 h, maximum plasma concentration (Cmax) of 31.9 +/- 1.5 mug/mL was attained at (tmax) 1.1 +/- 0.2 h and the drug was eliminated with an elimination half-life (t(1/2el)) of 2.06 +/- 0.11 h. The systemic bioavailability (F) after i.m. administration of cefepime was 86.8 +/- 7.5%. The extent of plasma protein binding measured in vitro was 14.8 +/- 0.54%. The drug was detected in urine for 36 h postadministration by both routes.