Pharmacokinetics and bioavailability of nimesulide in goats

The pharmacokinetic properties and bioavailability of cyclooxygenase (COX)-2 selective nonsteroidal anti-inflammatory drug nimesulide were investigated in female goats following intravenous (i.v.) and intramuscular (i.m.) administration at a dose of 4 mg/kg BW. Blood samples were collected by jugular venipuncture at predetermined times after drug administration. Plasma concentrations of nimesulide were determined by a validated high-performance liquid chromatography method. Plasma concentration-time data were subjected to compartmental analysis and pharmacokinetic parameters for nimesulide after i.v. and i.m. administration were calculated according to two- and one-compartment open models respectively. Following i.v. administration, a rapid distribution phase was followed by the slower elimination phase. The half-lives during the distribution phase (t1/2alpha) and terminal elimination phase (t1/2beta) were 0.11+/-0.10 and 7.99+/-2.23 h respectively. The steady-state volume of distribution (Vd(ss)), total body clearance (ClB) and mean residence time (MRT) of nimesulide were 0.64+/-0.13 L/kg, 0.06+/-0.02 L/h/kg and 11.72+/-3.42 h respectively. After i.m. administration, maximum plasma concentration (Cmax) of nimesulide was 2.83+/-1.11 microg/mL attained at 3.6+/-0.89 h (tmax). Plasma drug levels were detectable up to 72 h. Following i.m. injection, the t1/2beta and MRT of nimesulide were 1.63 and 1.73 times longer, respectively, than the i.v. administration. The bioavailability of nimesulide was 68.25% after i.m. administration at 4 mg/kg BW. These pharmacokinetic data suggest that nimesulide given intramuscularly may be useful in the treatment of inflammatory disease conditions in goats.     

Barium selenate as a slow-release selenium preparation to pigs

Pregnant sows were injected subcutaneously (s.c.) or intramuscularly (i.m.) with a barium selenate suspension (0.5–1.0 mg Se/kg body weight (b.w.)) and together with control animals fed a commercial diet. No response to the injection was seen either in blood selenium levels or in glutathione peroxidase (GSH-Px) activity in the sows. There was, however, a significant difference in these parameters between piglets born from treated dams and control animals. This status was maintained during the nursing period. In another experiment pigs (20 kg b.w.) on a Se-deficient diet were injected s.c. and i.m. with barium selenate (2.5 mg Se/kg b.w.). The treated groups maintained their blood levels of selenium and GSH-Px activity, although the selenium values in the group treated intramuscularly started to decline after 4 weeks. Organ samples from both groups were equal with regard to selenium at the time of slaughter while the control group showed a rapid decline both in blood selenium levels and GHS-Px activity.     

Oral absorption and bioavailability of flumequine in veal calves

The oral absorption and bioavailability of flumequine was studied in 1-, 5- and 18-week-old calves following intravenous and oral administration of different formulations of flumequine (Flumix, Flumix C and pure flumequine). Increasing age had a negative influence on the Cmax after the administration of Flumix, based on a larger VD in the older calves. The Cmax decreased from 5.02 +/- 1.46 micrograms/ml in the first week to 3.28 +/- 0.42 micrograms/ml in the 18th week. Adding colistin sulfate to the flumequine formulation and administring pure flumequine mixed with milk replacer had a negative effect on the Cmax of flumequine after oral administration of 5 and 10 mg/kg body weight. The bioavailability of the orally administered flumequine formulations was 100% in all cases except after the administration of Flumix C, for which it was 75.9 +/- 18.2%. The urinary recovery of flumequine after intravenous injection of a 10% solution varied from 35.2 +/- 2.3% for Group B, to 41.2 +/- 6.3% for Group C. The dosage of 5 mg/kg body weight Flumix twice daily in 1-week-old veal calves is sufficient to reach therapeutic plasma concentrations, based on a MIC value of 0.8 micrograms/ml of the target bacteria. In older calves it is advisable to increase the dosage 7.5 or 10 mg/kg body weight every 12 hours. In combination with colistin sulfate it is also advisable to increase the dosage slightly because of the negative effect of the colistin sulfate on the Cmax of flumequine.     

Pharmacokinetic-pharmacodynamic integration of danofloxacin after intravenous, intramuscular and subcutaneous administration to rabbits

The pharmacokinetics of danofloxacin was studied following intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration of 6 mg/kg to healthy rabbits. Danofloxacin concentration were determined by high-performance liquid chromatography assay with fluorescence detection. Minimal inhibitory concentrations (MICs) assay of danofloxacin against 30 strains of Staphylococcus aureus from several European countries was performed in order to compute pharmacodynamic surrogate markers. The danofloxacin plasma concentration versus time data after i.v. administration could best be described by a two-compartment open model. The disposition of i.m. and subcutaneously administered danofloxacin was best described by a one-compartment model. The terminal half-life for i.v., i.m. and s.c. routes was 4.88, 6.70 and 8.20 h, respectively. Clearance value after i.v. dosing was 0.76 L/kg.h. After i.m. administration, the absolute bioavailability was mean (+/-SD) 102.34 +/- 5.17% and the Cmax was 1.87 mg/L. After s.c. administration, the absolute bioavailability was mean (+/-SD) 96.44 +/- 5.95% and the Cmax was 1.79 mg/L. Danofloxacin shows a favourable pharmacokinetics profile in rabbits reflected by parameters such as a long half-life and a high bioavailability. However, in consideration of the low AUC/MIC indices obtained, its use by i.m. and s.c. route against the S. aureus strains assayed in this study cannot be recommended given the risk for selection of first mutant subpopulations.     

Pharmacodynamics and pharmacokinetics of cefoperazone and cefamandole in dogs following single dose intravenous and intramuscular administration

The pharmacokinetics and intramuscular (i.m.) bioavailability of cefoperazone and cefamandole (20mg/kg) were investigated in dogs and the findings related to minimal inhibitory concentrations (MICs) for 90 bacterial strains isolated clinically from dogs. The MICs of cefamandole for Staphylococcus intermedius (MIC(90) 0.125 microg/mL) were lower than those of cefoperazone (MIC(90) 0.5 micro/mL) although the latter was more effective against Escherichia coli strains (MIC(90) 2.0 microg/mL vs. 4.0 microg/mL). The pharmacokinetics of the drugs after intravenous administrations were similar: a rapid distribution phase was followed by a slower elimination phase (t((1/2)lambda2) 84.0+/-21.3 min for cefoperazone and 81.4+/-9.7 min for cefamandole). The apparent volume of distribution and body clearance were 0.233 L/kg and 1.96 mL/kg/min for cefoperazone, 0.190 L/kg and 1.76 mL/kg/min for cefamandole. After i.m. administration the bioavailability and peak serum concentration of cefamandole (85.1+/-13.5% and 35.9+/-5.4 microg/mL) were significantly higher than cefoperazone (41.4+/-7.1% and 24.5+/-3.0 micog/mL), but not the serum half-lives (t(1/2el) 134.3+/-12.6 min for cefoperazone and 145.4+/-12.3 min for cefamandole). The time above MIC(90) indicated that cefamandole can be administered once daily to dogs for the treatment of staphylococcal infections (T>MIC for S. intermedius 23.8+/-0.3 and for Staphylococcus aureus 21.6+/-0.6h).     

Pharmacokinetic-pharmacodynamic integration of moxifloxacin in rabbits after intravenous, intramuscular and oral administration

The pharmacokinetics of moxifloxacin was studied following intravenous (i.v.), intramuscular (i.m.) and oral dose of 5 mg/kg to healthy white New Zealand rabbits (n = 6). Moxifloxacin concentrations were determined by HPLC assay with fluorescence detection. The moxifloxacin plasma concentration vs. time data after i.v. administration could best be described by a two-compartment open model. The disposition of i.m. and orally administered moxifloxacin was best described by a one-compartment model. The plasma moxifloxacin clearance (Cl) for the i.v route was (mean +/- SD) 0.80 +/- 0.02 L/h.kg. The steady-state volume of distribution (Vss) was 1.95 +/- 0.18 L/kg. The terminal half-life (t(1/2lambdaz)) was (mean +/- SD) 1.84 +/- 0.12, 2.09 +/- 0.05 and 2.15 +/- 0.07 h after i.v., i.m. and oral, respectively. Minimal inhibitory concentration (MIC) assays of moxifloxacin against different strains of S. aureus were performed in order to compute pharmacodynamic surrogate markers. From these data, it is concluded that a 5 mg/kg dose moxifloxacin would be effective by i.m. and oral routes in rabbits against bacterial isolates with MIC < or = 0.06 microg/mL and possibly for MIC < or = 0.12 microg/mL, but in the latter case a higher dose would be required.     

Pharmacokinetics of florfenicol and its major metabolite, florfenicol amine, in rabbits

The pharmacokinetics of florfenicol and its active metabolite florfenicol amine were investigated in rabbits after a single intravenous (i.v.) and oral (p.o.) administration of florfenicol at 20 mg/kg bodyweight. The plasma concentrations of florfenicol and florfenicol amine were determined simultaneously by an LC/MS method. After i.v. injection, the terminal half-life (t(1/2lambdaz)), steady-state volume of distribution, total body clearance and mean residence time of florfenicol were 0.90 +/- 0.20 h, 0.94 +/- 0.19 L/kg, 0.63 +/- 0.06 L/h/kg and 1.50 +/- 0.34 h respectively. The peak concentrations (C(max)) of florfenicol (7.96 +/- 2.75 microg/mL) after p.o. administration were observed at 0.90 +/- 0.38 h. The t(1/2lambdaz) and p.o. bioavailability of florfenicol were 1.42 +/- 0.56 h and 76.23 +/- 12.02% respectively. Florfenicol amine was detected in all rabbits after i.v. and p.o. administration. After i.v. and p.o. administration of florfenicol, the observed Cmax values of florfenicol amine (5.06 +/- 1.79 and 3.38 +/- 0.97 microg/mL) were reached at 0.88 +/- 0.78 and 2.10 +/- 1.08 h respectively. Florfenicol amine was eliminated with an elimination half-life of 1.84 +/- 0.17 and 2.35 +/- 0.94 h after i.v. and p.o. administration respectively.     

Intravenous and intramuscular pharmacokinetics of a single-daily dose of disodium-fosfomycin in cattle, administered for 3 days

Pharmacokinetic parameters of fosfomycin in cattle were determined after administration of buffered disodium fosfomycin either intravenously (i.v.) or intramuscularly (i.m.) at a dose of 20 mg/kg/day for 3 days. Calculated concentrations at time zero and maximum serum concentrations were 34.42 and 10.18 mug/mL, respectively. The variables determined, the elimination half-life of the drug remained unchanged during the 3 days ( = 1.33 +/- 0.3 h for the i.v. route and = 2.17 +/- 0.4 h for the i.m. route). Apparent volumes of distribution suggest moderated distribution out of the central compartment (V(darea) = 673 mL +/- 27 mL/kg and V(dss) = 483 +/- 11 mL/kg). Bioavailability after i.m. administration was 74.52%. Considering fosfomycin as a time-dependent antibacterial drug, plasma concentration vs. time profiles obtained in this study, suggest that clinically effective plasma concentrations of fosfomycin could be obtained for up to 8 h following i.v. administration and approximately 10 h after i.m. injection of 20 mg/kg, for susceptible bacteria. In addition to residue studies in milk and edible tissues, a series of clinical assessments, using fosfomycin at 20 mg/kg b.i.d. or t.i.d. are warranted before this antibacterial drug should be considered for use in cattle.     

Pharmacokinetics of ticarcillin in the loggerhead sea turtle (Caretta caretta) after single intravenous and intramuscular injections.

Three captive loggerhead sea turtles, Caretta caretta, were used in four trials, one i.v. and three i.m., to determine the pharmacokinetic properties of a single dose of ticarcillin. For the i.v. study, each turtle received a single 50 mg/kg dose and blood samples were collected at 0, 0.5, 1, 2, 4, 6, 8, and 12 hr and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 14 days after administration. For the i.m. study, each turtle received one of three dosages (25, 50, or 100 mg/kg) in a randomized complete block design and blood samples were collected at the same time intervals. Each trial was separated by a minimum of 28 days to allow for complete drug clearance. Drug concentration in plasma was determined by a validated liquid chromatography-mass spectrometry assay. For the i.v. study, the elimination half-life was 5.0 hr. The apparent volume of distribution and plasma clearance were 0.17 L/kg and 0.0218 L/hr/kg, respectively. For the i.m. study, mean time to maximum plasma concentrations ranged from 1.7 ( +/- 0.58) hr in the 50 mg/kg group to 3.7 (+/- 2.5) hr in the 100 mg/kg group. Mean bioavailability ranged from 45% ( +/- 15%) in the 50 mg/kg group to 58% (+/- 12%) in the 100 mg/kg group, and the mean residence time ranged from 7.5 ( +/- 2.6) hr in the 25 mg/kg group to 16 (+/- 6.8) hr in the 100 mg/kg group. Two turtles had slight alanine aminotransferase elevations that were not clinically apparent at two different dosages, but otherwise, blood chemistries were unaffected. Possible i.m. dosage regimens for loggerhead sea turtles are 50 mg/kg q24 hr or 100 mg/kg q48 hr. Liver enzymes should be monitored during treatment.     

Pharmacokinetics and bioavailability of spectinomycin after i.v., i.m., s.c. and oral administration in broiler chickens

A pharmacokinetic and bioavailability study of spectinomycin was conducted in healthy broiler chickens following administration of a single (50 mg/kg bw) intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) dose and oral doses of 50 and 100 mg/kg bw. Following i.v. administration, the elimination half-life (t1/2beta), mean residence time (MRT), volume of distribution at steady-state (Vd(ss)), volume of distribution based on the terminal phase (Vd(z)) and total body clearance (ClB) were 1.46+/-1.10 h, 1.61+/-1.05 h, 0.26+/-0.009 L/kg, 0.34 (0.30-0.38) L/kg and 2.68+/-0.017 mL/min/kg respectively. After i.m. and s.c. dosing, the Cmax was 152.76+/-1.08 and 99.77+/-1.04 microg/mL, achieved at 0.25 (0.25-0.50) and 0.25 (0.25-1.00) h, the t1/2beta was 1.65+/-1.07 and 2.03+/-1.06 h and the absolute bioavailability (F) was 136.1% and 128.8% respectively. A significant difference in Cmax (5.13+/-0.10, 14.26+/-1.12 microg/mL), t1/2beta (3.74+/-1.07, 8.93+/-1.13 h) and ClB/F (22.69+/-0.018, 10.14+/-0.018 mL/min/kg) were found between the two oral doses (50 and 100 mg/kg bw respectively), but there were no differences in the tmax [2.00 (2.00-4.00), 2.00 (2.00-2.00) h] and Vd(z)/F [6.95 (6.34-9.06), 7.98 (4.75-10.62) L/kg). The absolute bioavailability (F) of spectinomycin was 11.8% and 26.4% after oral administration of 50 and 100 mg/kg bw respectively.     

Pharmacokinetic profile and in vitro selective cyclooxygenase-2 inhibition by nimesulide in the dog

The pharmacokinetic properties and in vitro potency of nimesulide, a nonsteroidal anti-inflammatory drug (NSAID) were investigated in 8 or 10 dogs after intravenous (i.v.), intramuscular (i.m.) and oral (single and multiple dose) administrations at the nominal dose of 5 mg/kg. After i.v. administration, the plasma clearance was 15.3 +/- 4.2 mL/kg/h, the steady-state volume of distribution was low (0.18 +/- 0.011 L/kg) and the elimination half-life was 8.5 +/- 2.1 h. After i.m. administration, the terminal half-life was 14.0 +/- 5.3 h indicating a slow process of absorption with a maximum plasma concentration (6.1 +/- 1.5 microg/mL) at 10.9 +/- 2.1 h postadministration and the systemic bioavailability was 69 +/- 22%. After oral administration in fasted dogs, the maximal plasma concentration (10.1 +/- 2.7 microg/mL) was observed 6.1 +/- 1.6 h after drug administration, the plasma half-life was 6.2 +/- 1.9 h and the mean bioavailability was 47 +/- 12%. After daily oral administrations for 5 days, the average plasma concentration during the fifth dosage interval was 8.1 +/- 2.9 microg/mL and the overall bioavailability was 58 +/- 16%. The mean accumulation ratio was 1.27 +/- 0.4. In vitro nimesulide inhibitory potencies for cyclooxygenase (COX)-1 and COX-2 isoenzymes were determined using a whole blood assay. Canine clotting blood was used to test for inhibition of COX-1 activity and whole blood stimulated by lipopolysaccharide (LPS) was used to test for inhibition of COX-2 activity. The inhibitory concentration (IC50) for inhibition of COX-2 and COX-1 were 1.6 +/- 0.4 microM (0.49 +/- 0.12 microg/mL) and 20.3 +/- 2.8 microM (6.3 +/- 0.86 microg/mL) giving a nimesulide COX-1/COX-2 ratio of 12.99 +/- 3.41. It was concluded that at the currently recommended dosage regimen (5 mg/kg), the plasma concentration totally inhibits COX-2 and partly inhibits COX-1 isoenzyme.     

Bioavailability and pharmacokinetics of florfenicol in healthy sheep

A study on bioavailability and pharmacokinetics of florfenicol was conducted in 20 crossbred healthy sheep following a single intravenous (i.v.) and intramuscular (i.m.) doses of 20 and 30 mg/kg body weight (b.w.). Florfenicol concentrations in serum were determined by a validated high-performance liquid chromatography method with UV detection at a wavelength of 223 nm in which serum samples were spiked with chloramphenicol as internal standard. Serum concentration-time data after i.v. administration were best described by a three-compartment open model with values for the distribution half-lives (T(1/2alpha)) 1.51 +/- 0.06 and 1.59 +/- 0.10 h, elimination half-lives (T(1/2beta)) 18.83 +/- 6.76 and 18.71 +/- 1.85 h, total body clearance (Cl(B)) 0.26 +/- 0.03 and 0.25 +/- 0.01 L/kg/h, volume of distribution at steady-state (V(d(ss))) 1.86 +/- 0.11 and 1.71 +/- 0.20 L/kg, area under curve (AUC) 76.31 +/- 9.17 and 119.21 +/- 2.05 microg.h/mL after i.v. injections of 20 and 30 mg/kg b.w. respectively. Serum concentration-time data after i.m. administration were adequately described by a one-compartment open model. The pharmacokinetic parameters were distribution half-lives (T(1/2k(a) )) 0.27 +/- 0.03 and 0.25 +/- 0.09 h, elimination half-lives (T(1/2k(e) )) 10.34 +/- 1.11 and 9.57 +/- 2.84 h, maximum concentrations (C(max)) 4.13 +/- 0.29 and 7.04 +/- 1.61 microg/mL, area under curve (AUC) 67.95 +/- 9.61 and 101.95 +/- 8.92 microg.h/mL, bioavailability (F) 89.04% and 85.52% after i.m. injections of 20 and 30 mg/kg b.w. respectively.     

Pharmacokinetics of single doses of cefoxitin given by the intravenous and intramuscular routes to unweaned calves

Cefoxitin pharmacokinetics and bioavailability were studied in unweaned calves. The antibiotic was administered to nine calves intravenously (i.v.), to seven calves intramuscularly (i.m.) at 20 mg/kg and to eight calves i.m. at 20 mg/kg together with probenecid at 40 mg/kg. Serum concentration versus time data were analysed using statistical moment theory (SMT). The i.v. data were also fitted by a linear, open two-compartment model. The elimination half-life (t1/2) was 66.9 +/- 6.9 min (mean +/- SD) after i.v. and 81.0 +/- 10.9 min after i.m. administration. The t1/2 increased to 125.5 +/- 15.6 min by the co-administration of probenecid. The total body clearance (ClT) was 4.88 +/- 1.71 ml/min/kg and the volume of distribution (Vss) 0.3187 +/- 0.0950 l/kg. The mean residence time (MRT) was 68.2 +/- 12.3 min after i.v. and 118.6 +/- 16.8 min after i.m. injection and increased to 211.5 +/- 16.8 min by the co-administration of probenecid. The mean absorption time (MAT) was 50.6 min and the estimated bioavailability (F) of cefoxitin after i.m. administration was 73.8%. The cefoxitin protein binding ranged from 55.0 to 42.0% at concentrations from 2 to 50 micrograms/ml. The MIC90 values for cefoxitin were 6.25 micrograms/ml for E. coli and Salmonella group B isolates, 3.13 micrograms/ml for Salmonella group C and D and Pasteurella multocida. There were no statistically significant differences between the pharmacokinetic parameters calculated by SMT or compartmental analysis. SMT provided an additional independent parameter, the MRT, for characterization of drug disposition kinetics.     

Bioavailability of amoxycillin in pigs

Amoxycillin was administered to pigs intravenously (i.v.), intramuscularly (i.m.) and orally (p.o.), in a cross-over design to examine the bioavailability ( F ) of various drug formulations. These included: a sodium salt for reconstitution in water and administration i.v.; trihydrate salt in an oil base for intramuscular administration producing 'conventional' duration of plasma concentrations; a trihydrate salt in oil base giving prolonged (LA) duration, and a trihydrate powder for oral administration in solution. The concentration of amoxycillin in plasma was measured by high-performance liquid chromatography, and its pharmacokinetic variables were assessed for the individual pigs by use of non-compartmental methods.
  Following i.v. administration (8.6 mg/kg), amoxycillin was eliminated rapidly with a mean residence time ( MRT ) of 1.4 h. After i.m. administration of the conventional formulation (14.7 mg/kg), the plasma amoxycillin concentration peaked at 2 h at 5.1 μg/mL. The bioavailability was 0.83. Intramuscular administration (14.1 mg/kg) of the long acting formulation (i.m. LA), lead to two peaks in plasma at 1.3 and 6.6 h. The bioavailability was calculated to be 1.11. After p.o. administration to fasted pigs, peak concentration was reached after 1.9 h, and the bioavailability was 0.33. In fed pigs, the corresponding values were 3.6 h and 0.28. Data showed that treatment of respiratory tract diseases in pigs by p.o. dosing alone, may not be optimal, because of the relatively low bioavailability and the fact that infections often result in reduced feed and water consumption. A rational treatment regime for susceptible respiratory pathogens includes an initial i.m. injection, followed by p.o. dosing every 12 h. Alternatively, the long acting formulation may be administered i.m. in a dose of 15 mg/kg, which would lead to active plasma concentrations for approximately 48 h.     

Pharmacokinetics and bioavailability of trimethoprim-sulfamethoxazole in alpacas

The pharmacokinetics and bioavailability of trimethoprim-sulfamethoxazole (TMP-SMX) were studied in six healthy male-castrate alpacas (Lama pacos) after intravenous (i.v.) or oral (p.o.) drug administration of 15 mg/kg TMP-SMX using a crossover design with a 2-week washout period. After 90 days one group (n = 3) was given a p.o. dose of 30 mg/kg TMP-SMX and the other group (n = 3) was given a p.o. dose of 60 mg/kg TMP-SMX. After i.v. administration of 15 mg/kg of TMP-SMX the mean initial plasma concentration (C0) was 10.75 +/- 2.12 microg/mL for trimethoprim (TMP) and 158.3 +/- 189.3 microg/mL for sulfamethoxazole (SMX). Elimination half-lives were 0.74 +/- 0.1 h for TMP and 2.2 +/- 0.6 h for SMX. The mean residence times were 1.45 +/- 0.72 h for TMP and 2.8 +/- 0.6 h for SMX. The areas under the respective concentration vs. time curves (AUC) were 2.49 +/- 1.62 microg h/mL for TMP and 124 +/- 60 microg h/mL for SMX. Total clearance (Clt) for TMP was 21.63 +/- 9.85 and 1.90 +/- 0.77 mL/min kg for SMX. The volume of distribution at steady state was 2.32 +/- 1.15 L/kg for TMP and 0.35 +/- 0.09 L/kg for SMX. After intragastric administration of 15, 30 and 60 mg/kg the peak concentration (Cmax) of SMX were 1.9 +/- 0.8, 2.6 +/- 0.4 and 2.8 +/- 0.7 microg/mL, respectively. The AUC was 9.1 +/- 5, 25.9 +/- 3.3 and 39.1 +/- 4.1 microg h/mL, respectively. Based upon these AUC values and correcting for dose, the respective bioavailabilities were 7.7, 10.5 and 7.94%. Trimethoprim was not detected in plasma after intragastric administration. These data demonstrate that therapeutic concentrations of TMP-SMX are not achieved after p.o. administration to alpacas.     

Pharmacokinetics and bioavailability of cefquinome in healthy piglets

A study on bioavailability and pharmacokinetics of cefquinome in piglets was conducted after intravenous (i.v.) and intramuscular (i.m.) administrations of 2.0 mg/kg of body weight, respectively. Plasma concentrations were measured by high‐performance liquid chromatography assay with UV detector at 268‐nm wavelength. Plasma concentration–time data after i.v. administration were best fit by a two‐compartment model. The pharmacokinetic values were distribution half‐life 0.27 ± 0.21 h, elimination half‐life 1.85 ± 1.11 h, total body clearance 0.26 ± 0.08 L/kg·h, area under curve 8.07 ± 1.91 μg·h/mL and volume of distribution at steady state 0.46 ± 0.10 L/kg. Plasma concentration–time data after i.m. administration were also best fit by a two‐compartment model. The pharmacokinetic parameters were distribution half‐life 0.88 ± 0.42 h, elimination half‐life 4.36 ± 2.35 h, peak concentration 4.01 ± 0.57 μg/mL and bioavailability 95.13 ± 9.93%.     

日粮中不同那西肽和硫酸粘杆菌素水平对仔猪生产性能的影响

为研究日粮中不同那西肽与硫酸粘杆菌素水平及其组合对断奶仔猪生产性能的影响,笔者开展了本试验。试验采用2×2双因子试验设计,试验期为28d。试验结果表明：随着饲粮中那西肽添加量由2．5mg／kg增加到5．0mg／kg。仔猪平均日增重和平均日采食量均得到显著改善（P〈0．05）,但对饲料转化率和腹泻率的影响不显著（P〉0．05）;硫酸粘杆菌素对仔猪平均日增重、平均日采食量、饲料转化率和腹泻率的影响均不显著（P〉0．05）;那西肽和硫酸粘杆菌素未体现出显著的组合效应（P〉0．05）。     

Serum leptin and ghrelin levels in response to methylprednisolone injection in healthy dogs

The aim of this study was to investigate the effects of methylprednisolone treatment on serum leptin and ghrelin levels in healthy dogs (n=40). After 14 h of fasting, the dogs were injected intramuscularly with saline (control group) or methylprednisolone (1, 5 or 10mg/kg). Blood samples were collected prior to (baseline) and 2, 3, 4, 8, 12 and 24h subsequent to the treatments. Serum leptin and ghrelin were measured by radioimmunoassay. The mean baseline serum leptin and ghrelin were 2.5+/-0.1 ng/mL (n=40) and 35.0+/-2.1 pg/mL (n=40), respectively. In the control dogs, serum leptin, but not ghrelin levels showed a significant fluctuation during the 24h observation period. Serum leptin increased significantly (p<0.05-0.01) between 2 and 12h after 1mg/kg of methylprednisolone. Serum leptin levels showed biphasic response to 5mg/kg of methylprednisolone: its level decreased to 1.9+/-0.1 ng/mL (p<0.01) at 2h and increased at 12h (2.6+/-0.1 ng/mL) (p<0.01). In response to 10mg/kg of methylprednisolone, serum leptin levels decreased significantly (p<0.01) for 24h. Serum ghrelin levels decreased to 19+/-5 pg/mL at 2-3h (p<0.01) or increased to 87+/-18 pg/mL at 3-8h (p<0.05-0.01) after 1mg/kg of methylprednisolone or 10mg/kg of methylprednisolone, respectively. Serum ghrelin levels did not change at any time point during 24h observation period after 5mg/kg of methylprednisolone. There was a significant (p<0.001) inverse correlation (r=-0.635) between serum leptin and ghrelin levels. In conclusion, we found that methylprednisolone increases or decreases serum leptin and ghrelin levels depending upon its dose and there is a negative correlation between serum leptin and ghrelin levels after methylprednisolone administration.     

Pharmacokinetics of an ampicillin-sulbactam combination after intravenous and intramuscular administration to neonatal calves

The pharmacokinetics of a 2:1 ampicillin-sulbactam combination after intravenous (i.v.) and intramuscular (i.m.) injection at a single dose rate of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam) were studied in 10-day-old neonatal calves (n = 10). The plasma concentration-time data of both antibiotics were best fitted to an open two-compartment model after i.v. administration. After i.m. administration, an open two-compartment model demonstrated first order absorption. The apparent volumes of distribution of ampicillin and sulbactam, calculated by the area method, were 0.20+/-0.01 and 0.18+/-0.01 L/kg, respectively, and the total body clearances were 0.51+/-0.03 and 0.21+/-0.01 L/kg h. The elimination half-lives of ampicillin after i.v. and i.m. administration were 0.99+/-0.03 and 1.01+/-0.02 h, respectively, whereas for sulbactam the half-lives were 2.24+/-0.02 and 3.44+/-0.94 h. The bioavailability after i.m. injection was high and similar for both drugs (70.31+/-0.2% for ampicillin and 68.62+/-4.44% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.47+/-0.02 and 0.72+/-0.01 h, respectively) and peak concentrations were also similar but not proportional to the dose administered (17.88+/-0.91 mg/L of ampicillin and 12.92+/-0.79 mg/L of sulbactam). Both drugs had similar pharmacokinetic behaviour after i.m. administration. Since the plasma concentrations of sulbactam were consistently higher during the elimination phase of their disposition, consideration could be given to formulating the ampicillin-sulbactam combination in a ratio higher than 2:1.     

Pharmacokinetics and tissue residues of josamycin in fowls.

Josamycin is a macrolide antibiotic which is produced by fermentation of cultures of Streptomyces narbonensis. It was once administrated (18 mg/kg b. wt.) in fowls via intravenous, oral and intramuscular routes for determination of blood concentration, kinetic behaviour and bioavailability. Following a single intravenous injection, the blood concentration-time-curve indicated a two compartments open model with an elimination half life value (t1/2 beta) of 1.83 +/- 0.06 hours. Both oral and intramuscular routes showed higher values, i.e. 2.33 +/- 0.13 and 2.85 +/- 0.17 hours. The lower apparent volume of distribution of Josamycin in fowls than one liter/kg elucidate higher distribution in blood than in tissues. Systemic bioavailability after both oral and intramuscular administration, i.e. 33.88 +/- 2.4 and 27.28 +/- 1.46% respectively, showed lower absorption from site of i.m. application. Josamycin was administered (18 mg/kg b. wt.) intramuscularly and orally once daily for 5 consecutive days. The drug peaked in serum 1 hour (intramuscular) and 2 hours (orally) after each dose. The recorded results revealed that serum level of Josamycin was higher after oral application (29.98 +/- 1.92 micrograms/ml) than after i.m. application. The drug persisted in the lung tissues and fat for 72 hours after administration and disappeared from all body tissues 96 hours after the last dose of repeated administration.