Pharmacokinetics of pradofloxacin and doxycycline in serum, saliva, and tear fluid of cats after oral administration

The pharmacokinetic properties of pradofloxacin and doxycycline were investigated in serum, saliva, and tear fluid of cats. In a crossover study design, six cats were treated orally with a single dose of pradofloxacin (Veraflox^® Oral Suspension 2.5%) and doxycycline (Ronaxan^® 100 mg) at 5 mg/kg body weight. Following administration, samples of serum, saliva, and tear fluid were taken in regular intervals over a period of 24 h and analysed by turbulent flow chromatography/tandem mass spectrometry. All values are given as mean ± SD. Pradofloxacin reached a mean maximum serum concentration ( C _max) of 1.1 ± 0.5 μg/mL after 1.8 ± 1.3 h ( t _max). In saliva and tear fluid, mean C _max was 6.3 ± 7.0 and 13.4 ± 20.9 μg/mL, respectively, and mean t _max was 0.5 ± 0 and 0.8 ± 0.3 h, respectively. Doxycycline reached a mean C _max in serum of 4.0 ± 0.8 μg/mL after 4.3 ± 3.2 h. Whilst only at two time-points doxycycline concentrations close to the limit of quantification were determined in tear fluid, no detectable levels were found in saliva. The high concentrations of pradofloxacin in saliva and tear fluid are promising to apply pradofloxacin for the treatment of conjunctivitis and upper respiratory tract infections in cats. As doxycycline is barely secreted into these fluids after oral application the mechanisms of its clinical efficacy remain unclear.     

Pharmacokinetics, bioavailability and dosage regimen of sulphadiazine (SDZ) in camels (Camelus dromedarius)

The pharmacokinetics of sulphadiazine (SDZ) (100 mg/kg, body weight) were investigated in six camels ( Camelus dromedarius ) after intravenous (i.v.) and oral (p.o.) administration. Following i.v. administration, the overall elimination rate constant (β) was 0.029±0.001/h and the half-life ( t _½β) was 23.14±1.06 h. The apparent volume of distribution ( V d_(area)) was 0.790±0.075 L/kg and the total body clearance ( Cl _B) was 23.29±2.50 mL/h/kg. After p.o. administration, SDZ reached a peak plasma concentration ( C _max(cal.)) of 62.93±2.79 μg/mL at a post injection time of ( T _max(cal.)) 22.98±0.83 h. The elimination half-life was 19.79±1.22 h, not significantly different from that obtained by the i.v. route. The mean absorption rate constant (K_a) was 0.056±0.002 h⁻¹ and the mean absorption half-life ( t _½Ka) was 12.33±0.37 h. The mean availability ( F ) of sulphadiazine was 88.2±6.2%.
  To achieve and maintain therapeutically satisfactory plasma SDZ levels of 50 μg/mL, the priming and maintenance doses would be 80 mg/kg and 40 mg/kg intravenously and 90 mg/kg and 45 mg/kg orally, respectively, to be repeated at 24 h intervals.     

Pharmacokinetics of lidocaine in serum and milk of mature Holstein cows

The purpose of this study was to evaluate the pharmacokinetics of lidocaine in mature Holstein cows following an inverted L and caudal epidural nerve block. Plasma and milk concentrations were determined using high-performance liquid chromatography assay. Pharmacokinetic parameters were estimated using a noncompartmental method. Following administration via inverted L nerve block, serum T_max was 0.521 ± 0.226 h and serum C_max was 572 ± 207 ng/mL. Serum AUC was 1348 ± 335 ng·h/mL. Apparent serum t_½β was 4.19 ± 1.69 h and MRT was 5.13 ± 2.33 h with clearance uncorrected for the extent of absorption of 2.75 ± 0.68 L/kg/h. The last measurable time of lidocaine detection in serum was 8.5 ± 1.4 h with a mean concentration of 51 ± 30 ng/mL. Milk T_max was detected at 1.75 ± 0.46 h with C_max of 300 ± 139 ng/mL. Milk AUC till the last time was 1869 ± 450 ng·h/mL with the mean AUC milk to AUC serum ratio of 1.439 ± 0.374. The last measurable time of lidocaine detection in milk was 32.5 ± 16.2 h with a mean concentration of 46 ± 30 ng/mL. There was no detectable lidocaine concentration in any samples following caudal epidural administration.     

Pharmacokinetics and disposition of clenbuterol in the horse

The pharmacokinetics of clenbuterol (CLB) following a single intravenous (i.v.) and oral (p.o.) administration twice daily for 7 days were investigated in thoroughbred horses. The plasma concentrations of CLB following i.v. administration declined mono-exponentially with a median elimination half-life ( t _1/2k) of 9.2 h, area under the time–concentration curve ( AUC ) of 12.4 ng·h/mL, and a zero-time concentration of 1.04 ng/mL. Volume of distribution ( V _d) was 1616.0 mL/kg and plasma clearance ( Cl ) was 120.0 mL/h/kg. The terminal portion of the plasma curve following multiple p.o. administrations also declined mono-exponentially with a median elimination half-life ( t _1/2k) of 12.9 h, a Cl of 94.0 mL/h/kg and V _d of 1574.7 mL/kg. Following the last p.o. administration the baseline plasma concentration was 537.5 ± 268.4 and increased to 1302.6 ± 925.0 pg/mL at 0.25 h, and declined to 18.9 ± 7.4 pg/mL at 96 h. CLB was still quantifiable in urine at 288 h following the last administration (210.0 ± 110 pg/mL). The difference between plasma and urinary concentrations of CLB was 100-fold irrespective of the route of administration. This 100-fold urine/plasma difference should be considered when the presence of CLB in urine is reported by equine forensic laboratories.     

Plasma pharmacokinetics and urine concentrations of meropenem in ewes

The pharmacokinetics of meropenem was studied in five ewes after single i.v. and i.m. dose of 20 mg/kg bw. Meropenem concentrations in plasma and urine were determined using microbiological assay method. A two-compartment open model was best described the decrease of meropenem concentration in plasma after an i.v. injection. The drug was rapidly eliminated with a half-life of elimination ( t _{1/2 β} ) of 0.39 ± 0.30 h. Meropenem showed a small steady-state volume of distribution [ V _d(ss)] 0.055 ± 0.09 L/kg. Following i.m. injection, meropenem was rapidly absorbed with a t _1/2ab of 0.25 ± 0.04 h. The peak plasma concentration ( C _max) was 48.79 ± 8.83  μ g/mL was attained after 0.57 ± 0.13 h ( t _max). The elimination half-life ( t _1/2el) of meropenem was 0.71 ± 0.12 h and the mean residence time ( MRT ) was 1.38 ± 0.26 h. The systemic bioavailability (F) after i.m. injection was 112.67 ± 10.13%. In vitro protein-binding percentage of meropenem in ewe's plasma was 42.80%. The mean urinary recoveries of meropenem over 24 h were 83% and 91% of the administered dose after i.v. and i.m. injections respectively. Thus, meropenem is likely to be efficacious in the eradication of many urinary tract pathogens in sheep.     

Pharmacokinetics of oxytetracycline in the red pacu (Colossoma brachypomum) following different routes of administration

Oxytetracycline (OTC) pharmacokinetics were studied in the red pacu ( Colossoma brachypomum ) following intravenous (i.v.) and intramuscular (i.m.) administration at a dose of 5 mg/kg body weight. OTC plasma concentrations were determined by high-performance-liquid-chromatography (HPLC). A non-compartmental model was used to describe plasma drug disposition after OTC administration. Following i.m. administration, the elimination half-life ( t _½) was 62.65 ± 1.25 h and the bioavailability was 49.80 ± 0.01%. After i.v. administration the t _½ was 50.97 ± 2.99 h, the V d was 534.11 ± 38.58 mL/kg, and CI _b was 0.121 ± 0.003 mL/min.kg. The 5 mg/kg i.v. dose used in this experiment resulted in up to 48 h plasma concentrations of OTC above the reported MIC values for some strains of fish pathogens such as Aeromonas hydrophila , A. liquefaciens , A. salmonicida , Cytophaga columnaris , Edwardsiella ictaluri , Vibrio anguillarium , V. ordalii , V. salmonicida and Yeersinia ruckeri . These MIC values are below the susceptible range (4 μg/mL) listed by the National Committee for Clinical Laboratory Standards (NCCLS) as determined by the NCCLS susceptibility interpretive criteria.     

The effects of pentoxifylline infusion on plasma 6-keto-prostaglandin F1α and ex vivo endotoxin-induced tumour necrosis factor activity in horses

Pentoxifylline (7.5 mg/kg) was bolused intravenously to eight healthy horses and was immediately followed by infusion (1.5 mg/kg/h) for 3 h. Clinical parameters were recorded and blood samples were collected for 24 h. Plasma was separated and concentrations of pentoxifylline, its reduced metabolite I, and 6-keto-prostaglandin F_1α were determined. Heparinized whole blood was also incubated ex vivo with 1 ng Escherichi coli endotoxin/mL blood for 6 h before determination of plasma tumour necrosis factor activity. The peak plasma concentrations of pentoxifylline and metabolite I occurred at 15 min after bolus injection and were 9.2± 1.4 and 7.8± 4.3 μg/mL, respectively. The half-life of elimination ( t _½β) of pentoxifylline was 1.44 h and volume of distribution ( V d_area) was 0.94 L/kg. The mean plasma concentration of 6-keto-prostaglandin F_1α increased over time, with a significant increase occurring 30 min after the bolus administration. Ex vivo plasma endotoxin-induced tumour necrosis factor activity was significantly decreased at 1.5 and 3 h of infusion. These results indicate that infusion of pentoxifylline will increase 6-keto-prostaglandin F_1α and significantly suppress endotoxin-induced tumour necrosis factor activity in horses during the period of infusion.     

Pharmacokinetics of a single bolus intravenous, intramuscular and subcutaneous dose of disodium fosfomycin in horses

Pharmacokinetic parameters of fosfomycin were determined in horses after the administration of disodium fosfomycin at 10 mg/kg and 20 mg/kg intravenously (IV), intramuscularly (IM) and subcutaneously (SC) each. Serum concentration at time zero (C_S0) was 112.21 ± 1.27 μg/mL and 201.43 ± 1.56 μg/mL for each dose level. Bioavailability after the SC administration was 84 and 86% for the 10 mg/kg and the 20 mg/kg dose respectively. Considering the documented minimum inhibitory concentration (MIC₉₀) range of sensitive bacteria to fosfomycin, the maximum serum concentration (Cmax) obtained (56.14 ± 2.26 μg/mL with 10 mg/kg SC and 72.14 ± 3.04 μg/mL with 20 mg/kg SC) and that fosfomycin is considered a time-dependant antimicrobial, it can be concluded that clinically effective plasma concentrations might be obtained for up to 10 h administering 20 mg/kg SC. An additional predictor of efficacy for this latter dose and route, and considering a 12 h dosing interval, could be area under the curve AUC_0-12/MIC₉₀ ratio which in this case was calculated as 996 for the 10 mg/kg dose and 1260 for the 20 mg/kg dose if dealing with sensitive bacteria. If a more resistant strain is considered, the AUC_0-12/MIC₉₀ ratio was calculated as 15 for the 10 mg/kg dose and 19 for the 20 mg/kg dose.     

Pharmacokinetics of indomethacin in sheep after intravenous and intramuscular administration

The pharmacokinetics of indomethacin (1mg/kg) was determined in six adult sheep after intravenous (i.v.) and intramuscular (i.m.) injection. Plasma concentrations were maintained within the therapeutic range (0.3–3.0 μg/mL) from 5 to 50 min after i.v. and from 5 to 60–90 min after i.m. administration. After two trials, indomethacin best fitted an open two-compartment model. The mean (±SD) volumes of distribution at steady state ( V d_ss) were 4.10 ± 1.40 and 4.21 ± 1.93 L/kg and the mean clearance values ( C l_B) were 0.17 ± 0.06 and 0.22 ± 0.12 L/h.kg for i.v. and i.m. routes, respectively. The elimination phase half-lives did not show any significant difference between routes of injection ( t _½β = 17.4 ± 4.6 and 21.25 ± 4.44 h, i.v. and i.m. respectively). After i.m. administration, plasma maximum concentration ( C _max =  1.10 ± 0.68 μg/mL) was reached 10 min after dosing; the absorption phase was fast ( K _ab = 26 ± 18 h-1) and short ( t _½ab = 2.33 ± 1.51 min) and the mean bioavailability was 91.0 ± 32.8%, although there was considerable interanimal variation. In some individuals, bioavailability was higher than 100%. This fact combined with the slower elimination phase after i.m. than after i.v. administration, could be related with enterohepatic recycling.     

Pharmacokinetics of phenylbutazone in plasma and milk of lactating dairy cows

Phenylbutazone was administered intravenously (i.v.) to a group of four lactating cows at a dosage of 6 mg/kg body weight. Whole plasma, protein-free plasma and milk were analysed for phenylbutazone residues. Pharmacokinetic parameters of total and free phenylbutazone in plasma were calculated using a non compartmental method. In regards to whole plasma data, the mean volume of distribution at steady state ( V _ss), was 147 mL/kg body weight, with a mean (± SEM) terminal elimination half-life ( t _1/2) of 40 ± 6 h. The mean clearance ( Cl ) was 3 mL/h/kg body weight. The V _ss as determined from the protein-free plasma fraction was 50 021 mL/kg body weight. This larger V _ss of free phenylbutazone compared to total plasma phenylbutazone was attributed to a high degree of plasma protein binding, as well as the greater penetration of free phenylbutazone into tissues. The mean t _1/2 of free phenylbutazone was 39 ± 5 h. This similarity to the t _1/2 estimated from total plasma phenylbutazone data is attributed to an equilibrium between free and plasma phenylbutazone during the terminal elimination phase. Mean t _1/2 as determined from milk, applying a urinary excretion rate model, was 47 ± 4 h. Milk clearance of phenylbutazone was 0.009 mL/h/kg body weight, or about 0.34% of total body clearance. Furthermore, evidence suggests that phenylbutazone either binds to milk proteins, or is actively transported into milk, as its concentration in milk was greater than that predicted due to a simple partitioning from plasma into milk.     

Kinetics and residues after intraperitoneal procaine penicillin G administration in lactating dairy cows

This paper describes the pharmacokinetic profile of procaine penicillin G after intraperitoneal (IP) administration in eight lactating dairy cows. Procaine pencillin G (PPG, 21 000 IU/kg) was deposited into the abdominal cavity of each cow following an incision in the right paralumbar fossa. Blood and milk samples were taken over the following 10 days, at which point the cows were euthanized. Plasma, milk, muscle, liver, and kidney penicillin concentrations were determined by HPLC, with a limit of quantification of 5 ng/mL for plasma and milk and 40 ng/g for tissue samples. A noncompartmental method was used to analyze plasma kinetics. The mean pharmacokinetic parameters (±SD) were: C _max, 5.5 ± 2.6 μg/mL; T _max, 0.75 ± 0.27 h; AUC _0-∞, 10.8 ± 4.9 μg·h/mL; MRT , 2.2 ± 0.9 h. All milk from treated cows contained detectable penicillin residues for a minimum of three milkings (31 h) and maximum of five milkings (52 h) after administration. Concentrations of penicillin in all muscle, liver, and kidney samples taken 10 days postadministration were below the limit of quantification. Necropsy examinations revealed foci of hemorrhage on the rumenal omentum of most cows but peritonitis was not observed. Systemic inflammation as determined by change in leukogram or plasma fibrinogen was noted in one cow. The results of this study demonstrate that IP PPG is absorbed and eliminated rapidly in lactating dairy cows.     

Comparative pharmacokinetics of amikacin in Greyhound and Beagle dogs

The purpose of the study was to compare the pharmacokinetics of amikacin administered i.v., to Greyhound and Beagle dogs and determine amikacin pharmacokinetics administered subcutaneously to Greyhounds. Amikacin was administered i.v. at 10 mg/kg to six healthy Greyhounds and six healthy Beagles. The Greyhounds also received amikacin, 10 mg/kg s.c. Plasma was sampled at predetermined time points and amikacin concentrations determined by a fluorescence polarization immunoassay (FPIA).
The volume of distribution was significantly smaller in Greyhounds (mean = 176.5 mL/kg) compared to Beagles (234.0 mL/kg). The C ₀ and AUC were significantly larger in Greyhounds (86.03 μg/mL and 79.97 h·μg/mL) compared to Beagles (69.97 μg/mL and 50.04 h·μg/mL). The plasma clearance was significantly lower in Greyhounds (2.08 mL/min/kg) compared to Beagles (3.33 mL/min/kg). The fraction of the dose absorbed after s.c. administration to Greyhounds was 0.91, the mean absorption time was 0.87 h, and the mean maximum plasma concentration was 27.40 μg/mL at 0.64 h.
Significant differences in the pharmacokinetics of amikacin in Greyhounds indicate it should be administered at a lower dose compared to Beagles. The dose in Greyhounds to achieve a C _max: AUC  ≥ 8 for bacteria (with an MIC  ≤ 4 μg/mL) is 12 mg/kg q24 h compared to 22 mg/kg q24 in Beagles.     

Disposition of metronidazole in hens (Gallus gallus) and quails (Coturnix coturnix japonica): pharmacokinetics and whole-body autoradiography

Hens were given single intravenous or oral doses (30 mg/kg body weight) of metronidazole and the plasma concentrations of the drug were determined by high-performance liquid chromatography (HPLC) at intervals from 10 min to 24 h after drug administration. Pharmacokinetic variables were calculated by the Lagrange algorithm technique. The elimination half-life ( t _1/2β) after the intravenous injection was 4.2 ± 0.5 h, the volume of distribution ( V _d(ss)) 1.1±0.2 L/kg and the total body clearance ( Cl _B) 131.2 ± 20 mL/h.kg. Oral bioavailability of the metronidazole was 78 ± 16%. The plasma maximum concentration ( C _max) 31.9 ± 2.3 μg/mL was reached 2 h after the oral administration and the oral elimination half-life ( t ₁/2β) was 4.7 ± 0.2 h. The binding of metronidazole to proteins in hen plasma was very low (less than 3%). Whole body autoradiography of [³H] metronidazole in hens and quails showed an even distribution of labelled material in various tissues at short survival intervals (1-4 h) after oral or intravenous administration. A high labelling was seen in the contents of the small and large intestines. In the laying quails a labelling was also seen in the albumen and in a ring in the periphery of the yolk at long survival intervals. Our results show that a concentration twofold above the MIC is maintained in the plasma of hens for at least 12 h at an oral dose of 30 mg/kg metronidazole.     

Influence of Pasteurella multocida infection on the pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in rabbits

Abo-El-Sooud, K., Goudah, A. Influence of Pasteurella multocida infection on the pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in rabbits. J. vet. Pharmacol. Therap. 33 , 63–68.
The pharmacokinetic behavior of marbofloxacin was studied in healthy ( n  = 12) and Pasteurella multocida infected rabbits ( n  = 12) after single intravenous (i.v.) and intramuscular (i.m.) administrations. Six rabbits in each group (control and diseased) were given a single dose of 2 mg/kg body weight (bw) of marbofloxacin intravenously. The other six rabbits in each group were given the same dose of the drug intramuscularly. The concentration of marbofloxacin in plasma was determined using high-performance liquid chromatography. The plasma concentrations were higher in diseased rabbits than in healthy rabbits following both routes of injections. Following i.v. administration, the values of the elimination half-life ( t _1/2β), and area under the curve were significantly higher, whereas total body clearance was significantly lower in diseased rabbits. After i.m. administration, the elimination half-life ( t _1/2el), mean residence time, and maximum plasma concentration ( C _max) were higher in diseased rabbits (5.33 h, 7.35 h and 2.24 μg/mL) than in healthy rabbits (4.33 h, 6.81 h and 1.81 μg/mL, respectively). Marbofloxacin was bound to the extent of 26 ± 1.3% and 23 ± 1.6% to plasma protein of healthy and diseased rabbits, respectively. The C _max /MIC (minimum inhibitory concentration) and AUC/MIC ratios were significantly higher in diseased rabbits (28 and 189 h) than in healthy rabbits (23 and 157 h), indicating the favorable pharmacodynamic characteristics of the drug in diseased rabbits.     

Effect of experimental renal impairment on disposition of marbofloxacin and its metabolites in the dog

The pharmacokinetics of marbofloxacin was studied in eight healthy female Beagle dogs before and after moderate renal impairment was induced experimentally. A single intravenous (i.v.) administration and repeated administration for 8 days (2 mg/kg, once-a-day) of marbofloxacin were studied. Renal impairment was induced by a right kidney nephrectomy and electrocoagulation of the left kidney. An increase ( P  < 0.001) in the plasma concentrations of urea (from 3.8 ± 0.7 to 9.8 ± 2.1 mmol/L) and creatinine (from 78.8 ± 3.4 to 145.8 ± 22.3 μmol/L), and a significant decrease (2.9 ± 0.3 vs 1.5 ± 0.2 mL/kg/min) ( P  < 0.001) in glomerular filtration rate were observed in the renal-impaired dogs. The clearance of marbofloxacin was slightly decreased after the induction of renal failure (1.6 ± 0.2 to 1.4 ± 0.1 mL/kg/min) ( P  < 0.05), but no significant variation of volume of distribution at steady state ( V _ss) and mean residence time ( MRT ) was observed after intravenous administration of marbofloxacin ( P > 0.05). Following oral administration of marbofloxacin, an increase in total area under the concentration time curve ( AUC ) was observed after renal failure (from 10372 ± 1710 to 11459 ± 1119 mg.min/L) ( P  < 0.05), but indices of accumulation were not modified. An increase ( P  < 0.01) in the AUC of N-oxide-marbofloxacin was observed after surgery. In conclusion, renal impairment has no biologically relevant influence on marbofloxacin disposition and there is no need for dosage adjustment of marbofloxacin in dogs with mild renal impairment.     

Pharmacokinetic parameters and milk concentrations of ketoprofen after administration as a single intravenous bolus dose to lactating goats

Six clinically normal lactating does were administered ketoprofen (2.2 mg/kg intravenously (i. v.)). Blood and milk samples were collected prior to and for 24 h after drug administration. Drug concentrations in serum and milk were determined by high performance liquid chromatography. Pharmacokinetic parameters from each goat were combined to obtain mean estimates (mean ± SD) of half-life of elimination ( t _½β) of 0.32 ± 0.14 h, systemic clearance ( Cl ) of 0.74 ± 0.12 L/kg· h, and volume of distribution at steady state ( V _ss) of 0.23 ± 0.051 L/kg. In milk, ketoprofen was unmeasurable by the method employed (level of detection 25 ng/mL) for all samples.     

Pharmacokinetics, metabolism and urinary detection time of flunixin after intravenous administration in camels

The pharmacokinetics of flunixin were determined after an intravenous dose of 1.1 mg/kg body weight in six camels and 2.2 mg/kg body weight in four camels. The data obtained (mean ±  SEM) for the low and high dose, respectively, were as follows:
  The elimination half-lives ( t _½β) were 3.76 ± 0.24 and 4.08 ± 0.49 h, the steady state volumes of distribution ( V d_ss) were 320.61 ± 38.53 and 348.84 ± 35.36 mL/kg body weight, total body clearances ( Cl _T) were 88.96 ± 6.63 and 84.86 ± 4.95 mL/h/kg body weight and renal clearances ( Cl _r) were 0.52 ± 0.09 and 0.62 ± 0.18 mL/h/kg body weight. A hydroxylated metabolite of flunixin was identified by gas chromatography/mass spectrometry (GC/MS) under electron and chemical ionization and its major fragmentation pattern was verified by tandem mass spectrometry (GC/MS/MS) using neutral loss, daughter and parent scan modes. The detection times for flunixin and its hydroxylated metabolite in urine after an intravenous (i.v.) dose of 2.2 mg/kg body weight were 96 and 48 h, respectively.     

Pharmacokinetics and bioavailability of doxycycline in turkeys

The pharmacokinetic parameters of doxycycline (DOX) were determined in 3 day, 3-, 6- and 12-week-old fasted turkeys, after a single intravenous (i.v.) dose of 25 mg doxycycline. HCl/kg body weight. Doxycycline disposition fitted an open two-compartment model. The mean (± SD) elimination half-life was 10.6 ± 0.7, 10.8 ± 1.5, 7.9 ± 1.4 and 10.0 ± 0.9 h in 3 day, 3-, 6- and 12-week-old turkeys, respectively. Mean (± SD) total body clearance was 0.19 (± 0.01), 0.27 (± 0.03), 0.11 (± 0.03) and 0.06 (± 0.01) L/h.kg in 3 day, 3-, 6- and 12-week-old turkeys, respectively. The steady-state volume of distribution was 1.77 (± 0.2), 2.1 (± 0.2), 0.7 (± 0.4) and 0.5 (± 0.2) L/kg in turkeys of the above mentioned ages, respectively. The AUC value significantly increased with the age of the turkeys. An oral doxycycline solution at a single dose of 25 mg/kg of body weight was administered to 3 day, 3-, 6- and 12-week-old turkeys. The maximal plasma concentrations in fasted turkeys were 3.8, 5.6, 7.4 and 5.7 μg/mL, with t _max values of 4.7, 1.5, 2.8 and 5.4 h, for the different ages, respectively. In fed turkeys the C _max values were 2.5, 6.1, 4.8 and 3.0 μg/mL, with t _max values of 4.2, 5.3, 4.5 and 7.5 h, respectively. The absolute bioavailability in fasted turkeys varied between 25.0 ± 9.0% (for 12-week-old birds) and 63.5 ± 7.1% (for 3-week-old birds). The relative bioavailability varied between 40.0 ± 13.0% (for 12-week-old birds) and 83.7 ± 14.3% (for 3-week-old birds).     

Attenuation of acute plasma cortisol response in calves following intravenous sodium salicylate administration prior to castration

Pain associated with castration in cattle is an animal welfare concern in beef production. This study examined the effect of oral aspirin and intravenous (i.v.) sodium salicylate on acute plasma cortisol response following surgical castration. Twenty bulls, randomly assigned to the following groups, (i) uncastrated, untreated controls, (ii) castrated, untreated controls, (iii) 50 mg/kg sodium salicylate i.v. precastration and (iv) 50 mg/kg aspirin (acetylsalicylic acid) per os precastration, were blood sampled at 3, 10, 20, 30, 40, 50 min and 1, 1.5, 2, 4, 6, 8, 10 and 12 h postcastration. Samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay for cortisol and salicylate, respectively. Data were analyzed using noncompartmental analysis, a simple cosine model, anova and t -tests. Intravenous salicylate V _d(ss) was 0.18 L/kg, Cl _B was 3.36 mL/min/kg and t _{1/2 λ} was 0.63 h. Plasma salicylate concentrations above 25  μ g/mL coincided with significant attenuation in peak cortisol concentrations ( P  = 0.029). Peak salicylate concentrations following oral aspirin administration was <10  μ g/mL and failed to attenuate cortisol response. Once salicylate concentrations decreased below 5  μ g/mL, cortisol response in the castrated groups was significantly higher than uncastrated controls ( P  = 0.018). These findings have implications for designing drug regimens to provide analgesia during routine animal husbandry procedures.     

Plasma and urine disposition and dose proportionality of ceftiofur and metabolites in dogs after subcutaneous administration of ceftiofur sodium

Nine male dogs (10.3–13.5 kg body weight) were randomly assigned to three groups of three dogs each and administered ceftiofur sodium subcutaneously as a single dose of 0.22, 2.2, or 4.4 mg ceftiofur free acid equivalents/kg body weight. Plasma and urine samples were collected serially for 72 h and assayed for ceftiofur and metabolites (derivatized to desfuroylceftiofur acetamide) using high-performance liquid chromatography. Urine concentrations remained above the MIC ₉₀ for Escherichia coll (4.0 μg/mL) and Proteus mirabilis (1.0 μg/mL) for over 24 h after doses of 2.2 mg/kg (8.1 μg/mL) and 4.4 mg/kg (29.6 μg/mL), the interval between treatments for ceftiofur sodium in dogs, whereas urine concentrations 24 h after dosing at 0.22 mg/kg (0.1 mg/Ib) were below the MIC ₉₀ for E.coli and P. mirabills (0.6 μg/mL). Plasma concentrations were dose-proportional, with peak concentrations of 1.66 ± 0.0990 μg/mL, 8.91 ± 6.42 μg/mL, and 26.7 ± 1.07 μg/mL after doses of 0.22, 2.2, and 4.4 mg/kg, respectively. The area under the plasma concentration versus time curve, when normalized to dose, was similar across all dosage groups.