Pharmacokinetics and bioavailability of valnemulin in Muscovy ducks (Cairina moschata)

1. A pharmacokinetic study of valnemulin was conducted in healthy Muscovy ducks after intravenous (IV), intramuscular (IM) and oral administrations at a dose rate of 15?mg/kg body weight.

2. Drug concentrations in plasma were determined by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetics parameters of valnemulin were analysed by compartmental analysis using the WinNonlin program.

3. After IV administration, valnemulin was widely distributed with a volume of distribution based on a terminal phase (V_z) of 8·19?±?3·07?l/kg, a mean elimination half-life (t_1/2Ke) of 2·63?h, and a clearance (Cl) value of 5·56?±?1·53?l/kg/h. Following intramuscular and oral administration, valnemulin was rapidly absorbed; the C_max was 0·44?±?0·13 and 0·12?±?0·02?µg/ml (achieved at 0·28 and 1·80?h), the t_1/2Ke was 3·17?±?3·83 and 4·83?±?1·81?h, and the absolute bioavailability (F) was 72% and 37%, respectively.

4. The plasma profile of valnemulin exhibited favourable pharmacokinetic characteristics in Muscovy ducks, such as wide distribution, and rapid absorption and elimination, though oral bioavailability was low.     

Pharmacokinetic analysis of cefquinome in healthy chickens

1. The pharmacokinetics of cefquinome (CEQ) in chickens was determined after intravenous (IV) and intramuscular (IM) administration of 2?mg/kg body weight. Plasma concentrations were measured by high performance liquid chromatography assay with an ultraviolet detector at 265?nm wavelength.

2. Plasma concentration–time data after IV administration were best fitted by a two-compartment model. The pharmacokinetic parameters following IV injection were distribution half-life 0·43?±?0·19?h, elimination half-life 1·29?±?0·10?h, total body clearance 0·35?±?0·04?l/kg/h, area under curve 5·33?±?0·55?µg/h/ml and volume of distribution at steady state 0·49?±?0·05?l/kg.

3. Plasma concentration–time data after IM administration were best described by a two-compartment model. The pharmacokinetic parameters after IM administration were absorption half-life 0·07?±?0·02?h, distribution half-life 0·58?±?0·27?h, elimination half-life 1·35?±?0·20?h, peak concentration 3·04?±?0·71?µg/ml and bioavailability 95·81?±?5·81%.

4. Cefquinome kinetics in chicken and data from other species were summarised and analysed to provide a comprehensive understanding of CEQ pharmacokinetics.     

Pharmacokinetics of levofloxacin in Japanese quails (Coturnix japonica) following intravenous and oral administration

1. The pharmacokinetics of levofloxacin were investigated in Japanese quails after a single dose of 10?mg/kg BW, given either intravenously or orally.

2. Following intravenous administration, the mean value of distribution at steady state (Vd_ss), total body clearance (Cl_tot) and mean residence time (MRT) of levofloxacin were 1·25?l/kg, 0·39?l/h/kg and 2·72?h, respectively.

3. Following oral administration of levofloxacin, the peak plasma concentration (C_max) was 3·31?µg/ml and was achieved at a maximum time (T_max) of 2?h. Mean residence time (MRT), mean absorption time (MAT) and bioavailability were 4·26?h, 1·54?h and 69·01%, respectively. In vitro plasma protein binding of levofloxacin was 23·52%.

4. Based on pharmacokinetic and pharmacodynamic integration, an oral dose of 10?mg/kg levofloxacin for every 12?h is recommended for a successful clinical effect in quails.     

Comparative pharmacokinetics of orbifloxacin in healthy and Pasteurella multocida infected ducks

1. The pharmacokinetic aspects of orbifloxacin were studied in both healthy and naturally diseased ducks after a single intravenous and intramuscular dose of 5?mg?kg^?1 body weight. The serum concentrations of orbifloxacin following single intravenous and intramuscular injections were higher in diseased than in healthy ducks.

2. The disposition of orbifloxacin after a single intravenous injection was described by a two-compartment open model in both healthy and diseased ducks. Orbifloxacin was distributed and eliminated at a significantly slower rate in diseased than in healthy ducks. The total body clearance (Cl_B) was lower in diseased (0·131?l?kg^?1?h^?1) than healthy ducks (0·191?l?kg^?1?h^?1).

3. Following intramuscular administration of orbifloxacin, the peak serum concentration (C_max) was higher in diseased than in healthy ducks, and this was achieved at a maximum time (t_max) of 1·114 and 0·993?h, respectively. The drug was eliminated at a significant slower rate in diseased ducks (elimination half-life t _{0·5( el )?}=?5·07?h) than in healthy ducks (elimination half-life t _{0·5( el )?}=?4·18?h).

4. These results indicate that drug elimination patterns in healthy and diseased ducks are not the same. The pharmacokinetic profile of the drug is altered in diseased ducks due to the increased serum orbifloxacin concentrations compared with clinically healthy ducks. In conclusion, 5?mg?kg^?1 body weight of orbifloxacin administered as a single dose once daily could be useful in the treatment of disease caused by Pasteurella multocida pathogen in ducks.     

Serum and tissue concentrations of doxycycline in broilers after the sub-cutaneous injection of a long-acting formulation

1. The antibacterial agent doxycycline hyclate (Dox) is usually administered to broilers in drinking water or as a feed supplement. Parenteral injection is not the usual route for administration, so a long-acting formulation (Dox-LA) was tested to evaluate if serum concentrations can achieve the pharmacokinetic/pharmacodynamic (PK/PD) ratios regarded as adequate for the drug.

2. A poloxamer-based matrix was used to provide Dox-LA. Serum and tissue concentrations of Dox vs time were determined in two day-old broilers after subcutaneous (SC) injection of Dox-LA or oral administration of a single bolus of aqueous Dox (Dox-PO), at a dose of 20?mg/kg. Weight gain, feed conversion rate, haematological variables, aspartate aminotransferase and alanine aminotransferase activities, blood urea and creatinine were determined and compared for Dox-LA with Dox-PO and non-medicated controls.

3. Dox-LA had a high relative bioavailability (1200%). Maximum serum concentrations were not statistically different (5·1?±?1·1?µg/ml for Dox-LA and 6·1?±?1.4?µg/ml for Dox-PO), but half-life of Dox-LA was much greater than the value obtained for Dox-PO (73·0?±?0·9?h and 2·0?±?0·02?h, respectively). Tissue concentrations were higher, and stayed higher for longer periods in the Dox-LA group.

4. In conclusion, considering the minimum effective serum concentration against Mycoplasma spp is 0·5?µg/ml, a dose-interval of 180?h can be achieved with Dox-LA, but only for 24?h after Dox-PO. Better PK/PD ratios for Dox-LA should result in improved clinical outcomes compared with Dox-PO.     

Pharmacokinetics and bioavailability of valnemulin in broiler chickens

Wang, R., Yuan, L.G., He, L.M., Zhu, L.X., Luo, X.Y., Zhang, C.Y., Yu, J.J., Fang, B.H., Liu, Y.H. Pharmacokinetics and bioavailability of valnemulin in broiler chickens. J. vet. Pharmacol. Therap. 34 , 247–251. The objective of this study was to investigate the pharmacokinetics and bioavailability of valnemulin in broiler chickens after intravenous (i.v.), intramuscular (i.m.) and oral administrations of 10 mg/kg body weight (bw). Plasma samples were analyzed by high‐performance liquid chromatography–tandem mass spectrometry (HPLC‐MS/MS). Pharmacokinetic characterization was performed by non‐compartmental analysis using WinNonlin program. After intravenous administration, distribution was wide with the volume of distribution based on terminal phase(V_z) of 4.27 ± 0.99 L /kg. Mean valnemulin t_1/2β(h), Cl_β(L /h /kg), V_ss (L /kg) and AUC_(0–∞)(μg·h /mL) values were 2.85, 0.99, 2.72 and 10.34, respectively. After intramuscular administration, valnemulin was rapidly absorbed with a C_max of 2.2 μg/mL achieved at 0.43 h (t_max), and the absolute bioavailability (F) was 88.81%; and for the oral route the same parameters were 0.66 ± 0.15 μg/mL, 1.54 ± 0.27 h and 74.42%. A multiple‐peak phenomenon was present after oral administration. The plasma profile of valnemulin exhibited a secondary peak during 2–6 h and a tertiary peak at 32 h. The favorable PK behavior, such as the wide distribution, slow elimination and acceptable bioavailability indicated that it is likely to be effective in chickens.     

Single-dose toxicokinetics of permethrin in broiler chickens

1. Single-dose toxicokinetics of permethrin was investigated in broiler chickens.

2. A total of 20 male broiler chickens were assigned at random to two groups of 10 at 30 days of age. A single dose of 10 mg/kg body weight of permethrin was administered intravenously to the first group; in the second group, the same dose was administered into the crop.

3. Serum permethrin was measured using an electron capture detector and gas chromatography equipment. The derived serum permethrin concentration/time curve demonstrated that the distribution kinetics of permethrin was well described by a two-compartment open model.

4. For intravenous permethrin administration, the half-life at λ phase (t_1/2λ), mean residence time (MRT) and area under the concentration–time curve in 0→∞ (AUC_0→∞) values respectively were 4.73 ± 1.00 h, 5.06 ± 1.05 h and 16.45 ± 3.28 mg/h/l. In contrast, the C_max, t_max, t_1/2λ, MRT and AUC_0→∞ values respectively of the group given intra-crop permethrin were 0.60 ± 0.42 μg/ml, 0.55 ± 0.19 h, 5.54 ± 0.78 h, 7.06 ± 0.63 h and 1.95 ± 0.97 mg/h/l. The bioavailability of permethrin was 0.11.

5. For both administration routes, the residence time of permethrin in the body was short and the bioavailability of permethrin was low. These results are relevant for assessing the use and safety of permethrin.

     

Pharmacokinetics following intravenous administration and pharmacodynamics of cefquinome in buffalo calves

Disposition following single intravenous injection (2 mg/kg) and pharmacodynamics of cefquinome were investigated in buffalo calves 6–8 months of age. Drug levels in plasma were estimated by high-performance liquid chromatography. The plasma concentration–time profile following intravenous administration was best described by a two-compartment open model. Rapid distribution of cefquinome was evident from the short distribution half-life (t _½α ?=?0.36?±?0.01 h), and small apparent volume of distribution (Vd_area?=?0.31?±?0.008 L/kg) indicated limited drug distribution in buffalo calves. The values of area under plasma concentration–time curve, elimination half-life (t _½β ), total body clearance (Cl_B), and mean residence time were 32.9?±?0.56 μg·h/mL, 3.56?±?0.05 h, 60.9?±?1.09 mL/h/kg, and 4.24?±?0.09 h, respectively. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration of cefquinome were 0.035–0.07 and 0.05–0.09 μg/mL, respectively. A single intravenous injection of 2 mg/kg may be effective to maintain the MIC up to 12 h in buffalo calves against the pathogens for which cefquinome is indicated.     

Comparative Pharmacokinetics of Gentamicin after Intravenous,Intramuscular, Subcutaneous and Oral Administration in Broiler Chickens

The pharmacokinetics and bioavailability of gentamicin sulphate (5 mg/kg body weight) were studied in 50 female broiler chickens after single intravenous (i.v.), intramuscular (i.m.), subcutaneous (s.c.) and oral administration. Blood samples were collected at time 0 (pretreatment), and at 5, 15 and 30 min and 1, 2, 4, 6, 8, 12, 24 and 48 h after drug administration. Gentamicin concentrations were determined using a microbiological assay and Bacillus subtillis ATCC 6633 as a test organism. The limit of quantification was 0.2 μg/ml. The plasma concentration–time curves were analysed using non-compartmental methods based on statistical moment theory. Following i.v. administration, the elimination half-life (t _1/2β), the mean residence time (MRT), the volume of distribution at steady state (V _ss), the volume of distribution (V _d,area) and the total body clearance (Cl_B) were 2.93 ± 0.15 h, 2.08 ± 0.12 h, 0.77 ± 0.05 L/kg, 1.68 ± 0.39 L/kg and 5.06 ± 0.21 ml/min per kg, respectively. After i.m. and s.c. dosing, the mean peak plasma concentrations (C _max) were 11.37 ± 0.73 and 16.65 ± 1.36 μg/ml, achieved at a post-injection times (t _max) of 0.55 ± 0.05 and 0.75 ± 0.08 h, respectively. The t _1/2β was 2.87 ± 0.44 and 3.48 ± 0.37 h, respectively after i.m. and s.c. administration. The V _d,area and Cl_B were 1.49 ± 0.21 L/kg and 6.18 ± 0.31 ml/min per kg, respectively, after i.m. administration and were 1.43 ± 0.19 L/kg and 4.7 ± 0.33 ml/min per kg, respectively, after s.c. administration. The absolute bioavailability (F) of gentamicin after i.m. administration was lower (79%) than that after s.c. administration (100%). Substantial differences in the resultant kinetics data were obtained between i.m. and s.c. administration. The in vitro protein binding of gentamicin in chicken plasma was 6.46%.     

Toxicokinetics of the broad-spectrum pyrethroid insecticide deltamethrin in broiler chickens

1. The aim of this study was to examine single-dose toxicokinetics of deltamethrin, a broad-spectrum pyrethroid insecticide, for treatment of broiler chickens.

2. Twenty male broiler chickens were used. Animals were divided into two groups, each comprising 10 animals. An intravenous dose of 0.75 mg of deltamethrin/kg body weight was given intravenously to the first group and the same dose (0.75 mg/kg body weight) was administered by intracrop by gavage to the second group. Blood samples were also collected at specified intervals.

3. Serum deltamethrin levels were measured via micro-electron capture detection with gas chromatography equipment. According to the serum deltamethrin level-time curve, deltamethrin tended to distribute according to a two-compartment open model.

4. The half-life at β phase (t_1/2β), mean residence time (MRT) and area under the concentration time curve in 0-∞ (AUC_0→∞) values after intravenous application of deltamethrin were 4.00 ± 0.76 h, 4.65 ± 0.75 h and 702.27 ± 236.07 ng h/ml, respectively. Furthermore, the absorption half-life (t_1/2a), maximal concentration in serum after intracrop administration (C_max), time needed to reach C_max (t_max), t_1/2β, MRT and AUC_0→∞ values after intracrop application of deltamethrin were determined to be 0.18 ± 0.06 h, 19.65 ± 4.58 ng/ml, 0.70 ± 0.10 h, 7.27 ± 1.36 h, 10.46 ± 1.84 h and 153.33 ± 30.83 ng h/ml, respectively. The bioavailability of deltamethrin was 21.83%.

5. It was concluded that deltamethrin was rapidly but incompletely absorbed after intracrop administration and bioavailability was at a low level. The t_1/2β and MRT of the deltamethrin were short for both intracrop and intravenous applications, and the risk of toxic and residual effects of deltamethrin is therefore limited.     

Comparative pharmacokinetics of diaveridine in pigs and chickens following single intravenous and oral administration

Comparative pharmacokinetic profiles of diaveridine following single intravenous and oral dose of 10 mg/kg body weight in healthy pigs and chickens were investigated, respectively. Concentrations of diaveridine in plasma samples were determined using a validated high‐performance liquid chromatography–ultraviolet (HPLC‐UV) method. The concentration–time data were subjected to noncompartmental kinetic analysis by WinNonlin program. The corresponding pharmacokinetic parameters in pigs or chickens after single intravenous administration were as follows, respectively: t_1/2β (elimination half‐life) 0.74 ± 0.28 and 3.44 ± 1.07 h; V_d (apparent volume of distribution) 2.70 ± 0.99 and 3.86 ± 0.92 L/kg; Cl_B (body clearance) 2.59 ± 0.62 and 0.80 ± 0.14 L/h/kg; and AUC_0‐∞ (area under the blood concentration vs. time curve) 4.11 ± 1.13 and 12.87 ± 2.60 μg?h/mL. The corresponding pharmacokinetic parameters in pigs or chickens after oral administration were as follows, respectively: t_1/2β 1.78 ± 0.41 and 2.91 ± 0.57 h; C_max (maximum concentration) 0.43 ± 0.24 and 1.45 ± 0.57 μg/mL; T_max (time to reach C_max) 1.04 ± 0.67 and 3.25 ± 0.71 h; and AUC_0‐∞1.33 ± 0.55 and 9.28 ± 2.69 μg?h/mL. The oral bioavailability (F) of diaveridine in pigs or chickens was determined to be 34.6% and 72.2%, respectively. There were significant differences between the pharmacokinetics profiles in these two species.     

Pharmacokinetics of difloxacin in healthy and E. coli-infected broiler chickens

1. The pharmacokinetics of difloxacin were investigated in healthy and E. coli-infected broiler chickens following intravenous and oral administration of a single dose of 10 mg/kg bodyweight.

2. After intravenous injection of difloxacin, the serum concentration–time curves were best described by a two-compartment open model. The distribution and elimination half-lives (t_0.5α) and (t_0.5el), respectively, were 0.10 ± 0.016 h and 3.7 ± 0.08 h in healthy chickens compared with 0.05 ± 0.005 h and 6.42 ± 0.71 h in E. coli-infected birds. The volumes of distribution V_dss were 3.14 ± 0.11 and 9.25 ± 0.43 l/kg, with total body clearance (Cl_tot) of 0.65 ± 0.018 and 1.14 ± 0.1 ml/kg/h, respectively.

3. Following oral administration, difloxacin was absorbed with t_0.5(ab) of 0.57 ± 0.06 and 0.77 ± 0.04 h and was eliminated with t_0.5(el) of 4.7 ± 0.34 and 3.42 ± 0.19, respectively, in normal and infected chickens. The peak serum concentrations were 1.34 ± 0.09 and 1.05 ± 0.06 µg/ml and attained a T_max of 2.27 ± 0.07 and 2.43 ± 0.06 h, respectively. The systemic bioavailability of difloxacin following oral administration was 86.2% in healthy chickens and 90.6% in E. coli-infected birds. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of difloxacin against the field strain of E. coli O78 in vitro were 0.02 µg and 0.04 µg/ml, respectively.

4. These results show that administration of a therapeutic dose of difloxacin is effective in the treatment of E. coli infection in chickens. The serum concentration of the drug was much higher than the MIC of the E. coli O78 strain in both healthy and infected chickens.     

Pharmacokinetics of erythromycin after the administration of intravenous and various oral dosage forms to dogs

The purpose of this study was to describe and compare the pharmacokinetic properties of different formulations of erythromycin in dogs. Erythromycin was administered as lactobionate (10 mg/kg, IV), estolate tablets (25 mg/kg p.o.) and ethylsuccinate tablets or suspension (20 mg/kg p.o.). After intravenous (i.v.) administration, the principal pharmacokinetic parameters were (mean ± SD): AUC_(0–∞) 4.20 ± 1.66 μg·h/mL; C_max 6.64 ± 1.38 μg/mL; V_z 4.80 ± 0.91 L/kg; Cl_t 2.64 ± 0.84 L/h·kg; t_½λ 1.35 ± 0.40 h and MRT 1.50 ± 0.47 h. After the administration of estolate tablets and ethylsuccinate suspension, the principal pharmacokinetic parameters were (mean ± SD): C_max, 0.30 ± 0.17 and 0.17 ± 0.09 μg/mL; t_max, 1.75 ± 0.76 and 0.69 ± 0.30 h; t_½λ, 2.92 ± 0.79 and 1.53 ± 1.28 h and MRT, 5.10 ± 1.12 and 2.56 ± 1.77 h, respectively. The administration of erythromycin ethylsuccinate tablets did not produce measurable serum concentrations. Only the i.v. administration rendered serum concentrations above MIC₉₀ = 0.5 μg/mL for 2 h. However, these results should be cautiously interpreted as tissue erythromycin concentrations have not been measured in this study and, it is recognized that they can reach much higher concentrations than in blood, correlating better with clinical efficacy.     

Toxicokinetics and absolute oral bioavailability of melamine in broiler chickens

The objective of this study was to investigate the toxicokinetic characteristics of melamine in broilers due to the limited information available for livestock. Melamine was then administered to broiler chickens at an intravenous (i.v.) or oral (p.o.) dosage of 5.5 mg/kg of body weight, and plasma samples were collected up to 48 h. The concentration of melamine in each plasma sample was analyzed using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Melamine was measurable up to 24 h after i.v. and p.o. administration. A one‐compartment model was developed to describe the toxicokinetics of melamine in broilers. Following i.v. administration, the values for the elimination half‐life (t_1/2β), the volume of distribution (V_d), and the clearance (CL) were 4.42 ± 1.02 h, 00.52 ± 0.18 L/kg, and 0.08 ± 0.01 L/h/kg, respectively. The absolute oral bioavailability (F) was 95.63 ± 3.54%. The results suggest that most of the administered melamine is favorably absorbed from the alimentary tract and rapidly cleared by the kidneys in broiler chickens.     

Changes in body temperature during growth and in response to fasting in growing modern meat type chickens

1. Rectal or core body temperature was determined in a study to examine the effects of fasting in modern meat type broilers at three stages of growth, namely d 19, 33 and 47.

2. There were two treatment groups: fed with feed available ad libitum and fasted. Rectal temperatures were determined at noon (1200?h). At that time, feed was removed from the fasted group. The body temperatures were then determined again after 6, 12, 18 and 24?h.

3. Core body temperatures decreased with fasting. The decrease was evident after as little as 6?h of fasting with a further decline evident by 12?h.

4. Accompanying the decrease in body temperature with fasting there were decreases in the venous concentrations of carbon dioxide in the blood and sodium in the plasma.

5. The decrease in both body temperature and carbon dioxide presumably reflects depressed metabolic rate.

6. Unexpectedly, the core body temperature increased progressively with age in the control fed group (d 19?=?41·04?±?0·02°C, d 33?=?41·65?±?0·05°C, d 47?=?42·21?±?0·12°C).

7. In the fed control group, core body temperatures were reduced at night, when feeding activity would be anticipated to be greatly reduced.     

Pharmacokinetics and bioavailability of sulfadiazine and trimethoprim following intravenous, intramuscular and oral administration in ostriches (Struthio camelus)

A pharmacokinetic and bioavailability study of sulfadiazine combined with trimethoprim (sulfadiazine/trimethoprim) was carried out in fifteen healthy young ostriches after intravenous (i.v.), intramuscular (i.m.) and oral administration at a total dose of 30 mg/kg body weight (bw) (25 and 5 mg/kg bw of sulfadiazine and trimethoprim, respectively). The study followed a single dose, three periods, cross‐over randomized design. The sulfadiazine/trimethoprim combination was administered to ostriches after an overnight fasting on three treatment days, each separated by a 2‐week washout period. Blood samples were collected at 0 (pretreatment), 0.08, 0.25, 0.50, 1, 2, 4, 6, 8, 12, 24 and 48 h after drug administration. Following i.v. administration, the elimination half‐life (t_1/2β), the mean residence time (MRT), volume of distribution at steady‐state (V_d(ss)), volume of distribution based on terminal phase (V_d(z)), and the total body clearance (Cl_B) were (13.23 ± 2.24 and 1.95 ± 0.19 h), (10.06 ± 0.33 and 2.17 ± 0.20 h), (0.60 ± 0.08, and 2.35 ± 0.14 L/kg), (0.79 ± 0.12 and 2.49 ± 0.14 L/kg) and (0.69 ± 0.03 and 16.12 ± 1.38 mL/min/kg), for sulfadiazine and trimethoprim, respectively. No significant difference in C_max (35.47 ± 2.52 and 37.50 ± 3.39 μg/mL), t_max (2.47 ± 0.31 and 2.47 ± 0.36 h), t_½β (11.79 ± 0.79 and 10.96 ± 0.56 h), V_d(z)/F (0.77 ± 0.06 and 0.89 ± 0.07 L/kg), Cl_B/F (0.76 ± 0.04 and 0.89 ± 0.07) and MRT (12.39 ± 0.40 and 12.08 ± 0.36 h) were found in sulfadiazine after i.m. and oral dosing, respectively. There were also no differences in C_max (0.71 ± 0.06 and 0.78 ± 0.10 μg/mL), t_max (2.07 ± 0.28 and 3.27 ± 0.28 h), t_½β (3.30 ± 0.25 and 3.83 ± 0.33 h), V_d(z)/F (6.2 ± 0.56 and 6.27 ± 0.77 L/kg), Cl_B/F (21.9 ± 1.46 and 18.83 ± 1.72) and MRT (3.68 ± 0.19 and 4.34 ± 0.14 h) for trimethoprim after i.m. and oral dosing, respectively. The absolute bioavailability (F) was 95.41% and 86.20% for sulfadiazine and 70.02% and 79.58% for trimethoprim after i.m. and oral administration, respectively.     

The pharmacokinetics of cefadroxil over a range of oral doses and animal ages in the foal

To evaluate the effect of foal age on the pharmacokinetics of cefadroxil, five foals were administered cefadroxil in a single intravenous dose (5 mg/kg) and a single oral dose (10 or 20 mg/kg) at ages of 0.5, 1, 2, 3 and 5 months. Pharmacokinetic parameters of terminal elimination rate constant (β_po), oral mean residence time (MRT_po), mean absorption time (MAT), rate constant for oral absorption (K_a), bioavailability F, peak serum concentrations(C_max) and time of peak concentration (t_max), were evaluated in a repeated measures analysis over dose. Across animal ages, parameters for the intravenous dose did not change significantly over animal age (P 0.05). Mean values ± SEM were: β_IV = 0.633 ± 0.038 h^?1; Cl = 0.316 ± 0.010 L/kg/h; V_c = 0.196 ± 0.008 L/kg; V_area = 0.526 ± 0.024 L/kg; V_SS =0.374 ± 0.014 L/kg; MRT_iv = 1.22 ± 0.07 h; K_el = 1.67 ± 0.08 ^h?1. Following oral administration, drug absorption became faster with age (P < 0.05), as reflected by MRT_po, MAT, K_a and t_max. However, oral bioavailability (±SE) declined significantly (P < 0.05) from 99.6 ± 3.69% at 0.5 months to 14.5 ± 1.40% at 5 months of age. To evaluate a dose effect on the pharmacokinetic parameters, a series of oral doses (5, 10, 20 and 40 mg/kg) were administered to these foals at 1 month of age. β_po (0.548 ± 0.023 h^?1) and F (68.26 ± 2.43%) were not affected significantly by the size of the dose. C_max was approximately doubled with each two-fold increase in dose: 3.15 ± 0.15, 5.84 ± 0.48, 12.17 ± 0.93 and 19.71 ± 2.19 μg/mL. Dose-dependent kinetics were observed in MRT_po, MAT, K_a and t_max.     

Plasma Concentrations,Pharmacokinetics and Urinary Excretion of Gatifloxacin after Single Intravenous Injection in Buffalo Calves

The pharmacokinetics and urinary excretion of gatifloxacin were investigated after a single intravenous injection of 4 mg/kg body weight in buffalo calves. The therapeutic plasma drug concentration was maintained for up to 12 h. Gatifloxacin rapidly distributed from blood to tissue compartments, which was evident from the high values of the distribution rate constant, α₁ (11.1 ± 1.06 h⁻¹) and the rate constant of transfer of drug from central to peripheral compartment, k ₁₂ (6.29 ± 0.46 h⁻¹). The area under the plasma drug concentration–time curve and apparent volume of distribution were 17.1 ± 0.63 (μg.h)/ml and 3.56 ± 0.95 L/kg, respectively. The elimination half-life (t _{1/2 β}), total body clearance (Cl_B) and the ratio of drug present in tissues and plasma (T/P) were 10.4 ± 2.47 h, 235.1 ± 8.47 ml/(kg.h) and 10.1 ± 2.25, respectively. About 19.7% of the administered drug was excreted in urine within 24 h. A satisfactory intravenous dosage regimen for gatifloxacin in buffalo calves would be 5.3 mg/kg at 24 h intervals. Abbreviations for pharmacokinetic parameters are given in the footnote of Table I     

Pharmacokinetics of oxytetracycline and therapeutic implications in veal calves

Pharmacokinetic parameters of oxytetracycline were analysed in healthy preruminant veal calves after intravenous, intramuscular and oral administration. The serum half-lives in the β-elimination phase of both 10% and 20% solutions after i.v. injection of 10 mg/kg were similar (7.07 ± 1.36 h and 7.16 ± 1.17 h, mean ± SD), whereas the total body clearance and the apparent volume of distribution were higher for the 20% solution. Serum concentrations above 0.5 μg/ml were maintained with both formulations during 12–24 h but were only above 4 μg/ml to 5 h. Intramuscular administration of the 20% solution gave a complete absorption with two rate constants of absorption, a faster (t_1/2a1= 0.27 h) and a slower one (t_1/2a2= 10.90 h) responsible for the delayed elimination half-life after this route of application (t_1/2β= 9.83 ± 1.35 h). Mean serum concentrations reached a maximum level of 3.01 ± 0.72 μg/ml at 4.01 ± 2.84 h and decreased to 0.5 μg/ml between 12 and 24 h. 50 mg/kg given orally with a milk replacer were found to have a mean bioavailability of 46.35%. A mean serum peak level of 4.99 ± 1.37 μg/ml was achieved at 9.16 ± 1.99 h and the mean concentration was still above 0.5 μg/ml after 48 h. The elimination half-life (t_1/2β= 10.66 ± 3.15 h) reflected the slow absorption step (t_1/2a2= 10.15 h) following that responsible for the initial faster absorption (t_1/2a2= 1.99 h). Comparison of the area under the serum curves gave mean values of 117% for tetracycline and of 53% for chlortetracycline relative to oxytetracycline (arbitrarily fixed at 100%) after identical oral dosage of the three tetracyclines. We also propose and discuss a dosage schedule based on minimal inhibitory concentrations of different susceptible pathogens     

Pharmacokinetics of sanguinarine,chelerythrine, and their metabolites in broiler chickens following oral and intravenous administration

Sanguinarine (SA) and chelerythrine (CHE) are the main active components of the phytogenic livestock feed additive, Sangrovit®. However, little information is available on the pharmacokinetics of Sangrovit® in poultry. The goal of this work was to study the pharmacokinetics of SA, CHE, and their metabolites, dihydrosanguinarine (DHSA) and dihydrochelerythrine (DHCHE), in 10 healthy female broiler chickens following oral (p.o.) administration of Sangrovit® and intravenous (i.v.) administration of a mixture of SA and CHE. The plasma samples were processed using two different simple protein precipitation methods because the parent drugs and metabolites are stable under different pH conditions. The absorption and metabolism of SA following p.o. administration were fast, with half‐life (t_1/2) values of 1.05 ± 0.18 hr and 0.83 ± 0.10 hr for SA and DHSA, respectively. The maximum concentration (C_max) of DHSA (2.49 ± 1.4 μg/L) was higher that of SA (1.89 ± 0.8 μg/L). The area under the concentration vs. time curve (AUC) values for SA and DHSA were 9.92 ± 5.4 and 6.08 ± 3.49 ng/ml hr, respectively. Following i.v. administration, the clearance (CL) of SA was 6.79 ± 0.63 (L·h^?1·kg^?1) with a t_1/2 of 0.34 ± 0.13 hr. The AUC values for DHSA and DHCHE were 7.48 ± 1.05 and 0.52 ± 0.09 (ng/ml hr), respectively. These data suggested that Sangrovit® had low absorption and bioavailability in broiler chickens. The work reported here provides useful information on the pharmacokinetic behavior of Sangrovit® after p.o. and i.v. administration in broiler chickens, which is important for the evaluation of its use in poultry.