Comparison of the oral bioavailability and tissue disposition of monensin and salinomycin in chickens and turkeys

Henri, J., Maurice, R., Postollec, G., Dubreil‐Cheneau, E., Roudaut, B., Laurentie, M., Sanders, P. Comparison of the oral bioavailability and tissue disposition of monensin and salinomycin in chickens and turkeys. J. Vet. Pharmacol. Therap.  35 , 73–81. The current study describes the pharmacokinetic parameters of two carboxylic polyether ionophores: monensin in turkeys and salinomycin in chickens. These data can be used to understand and predict the occurrence of undesirable residues of coccidiostats in edible tissues of these animal species. Special attention is paid to the distribution of residues between the different edible tissues during and at the end of the treatment period. For the bioavailability studies, monensin was administered to turkeys intravenously, in the left wing vein, at a dose of 0.4 mg /kg and orally at a dose of 20 mg /kg. Salinomycin was administered to chickens intravenously, in the left wing vein, at a dose of 0.25 mg /kg and orally at a dose of 2.5 mg /kg. Residue studies were carried out with supplemented feed at the rate of 100 mg /kg of feed for monensin in turkeys and 70 mg /kg for salinomycin in chickens, respectively. Coccidiostats had a low bioavailability in poultry (around 30% for monensin in chickens, around 1% for monensin in turkeys and around 15% for salinomycin in chickens). Monensin in chickens had a longer terminal half‐life (between 3.07 and 5.55 h) than both monensin in turkeys (between 1.36 and 1.55 h) and salinomycin in chickens (between 1.33 and 1.79 h). The tissue /plasma partition coefficients showed a higher affinity of both monensin and salinomycin for fat, followed by liver and muscle tissue. The depletion data showed a fairly rapid elimination of coccidiostats in all the tissues after cessation of treatment. According to the results of depletion studies, a withdrawal period of 1 day seems sufficient to avoid undesirable exposure of consumers.     

Naïve averaged, naïve pooled, and population pharmacokinetics of orally administered marbofloxacin in juvenile harbor seals

OBJECTIVE: To determine the pharmacokinetics of marbofloxacin after oral administration in juvenile harbor seals (Phoca vitulina) at a dose of 5 mg/kg (2.3 mg/lb) and to compare pharmacokinetic variables after pharmacokinetic analysis by na?ve averaged, na?ve pooled, and nonlinear mixed-effects modeling. DESIGN: Original study. Animals-33 male and 22 female juvenile seals being treated for various conditions. PROCEDURES: Blood collection was limited to < or = 3 samples/seal. Plasma marbofloxacin concentrations were measured via high-pressure liquid chromatography with UV detection. RESULTS: Mean +/- SE dose of marbofloxacin administered was 5.3 +/- 0.1 mg/kg (2.4 +/- 0.05 mg/lb). The terminal half-life, volume of distribution (per bioavailability), and clearance (per bioavailability) were approximately 5 hours, approximately 1.4 L/kg, and approximately 3 mL/min/kg, respectively (values varied slightly with the method of calculation). Maximum plasma concentration and area under the plasma-time concentration curve were approximately 3 microg/mL and 30 h x microg/mL, respectively. Na?ve averaged and na?ve pooled analysis appeared to yield a better fit to the population, but nonlinear mixed-effects modeling yielded a better fit for individual seals. CONCLUSIONS AND CLINICAL RELEVANCE: Values of pharmacokinetic variables were similar regardless of the analytic method used. Pharmacokinetic variability can be assessed with nonlinear mixed-effects modeling, but not with na?ve averaged or na?ve pooled analysis. Visual observation by experienced trainers revealed no adverse effects in treated seals. Plasma concentrations attained with a dosage of 5 mg/kg every 24 hours would be expected to be efficacious for treatment of infections caused by susceptible bacteria (excluding Pseudomonas aeruginosa).     

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.     

Pharmacokinetic profile and tissue distribution of monensin in broiler chickens

1. The pharmacokinetics of monensin, including half‐life, apparent volume of distribution, total body clearance, systemic bio‐availability and tissue residues were determined in broiler chickens. The drug was given by intracrop and intravenous routes in a single dose of 40 mg/kg body weight.

2. Following intravenous injection the kinetic disposition of monensin followed a two compartments open model with absorption half life of 0.59 h, volume of distribution of 4.11 I/kg and total body clearance of 28.36 ml/kg/min. The highest serum concentrations of monensin were reached 0.5 h after intracrop dosage with an absorption half‐life of 0.27 h and an elimination half life of 2.11 h. The systemic bioavailability was 65.1% after intracorp administration. Serum protein‐binding tendency of monensin calculated in vitro was 22.8%.

3. Monensin concentrations in the serum and tissues of chickens after a single intracrop dose of pure monensin (40 mg/kg body weight) were higher than those after feeding a supplemented monensin pre‐mix (120 mg/kg) for 2 weeks. Monensin residues were detected in tested body tissues, collected 2, 4, 6 and 8 h after oral administration. The highest conentration was found in the liver. In addition, monensin residues were detected only in liver, kidney and fat 24 h after the last oral dose. No monensin residues could be detected in tissues after 48 h, except in liver which cleared completely by 72 h.     

Pharmacokinetics of monepantel and its sulfone metabolite, monepantel sulfone, after intravenous and oral administration in sheep

The pharmacokinetic properties of the developmental Amino-Acetonitrile Derivative (AAD), monepantel and its sulfone metabolite, monepantel sulfone were investigated in sheep following intravenous (i.v.) and oral administrations. The sulfone metabolite was rapidly formed and predominated over monepantel 4 h after dosing, irrespective of the route of administration. The steady-state volume of distribution, total body clearance and mean residence time of monepantel were 7.4 L/kg, 1.49 L/(kg·h) and 4.9 h, respectively and 31.2 L/kg, 0.28 L/(kg·h) and 111 h, respectively for monepantel sulfone. The overall bioavailability of monepantel was 31%, but it was demonstrated that approximately the same amount of monepantel sulfone was produced whether monepantel was given intravenously or orally ( AUC _(0–∞) oral/ AUC _(0–∞) i.v. of 94% for monepantel sulfone), making oral administration a very efficient route of administration for monepantel in terms of the amount of sulfone metabolite generated. Because monepantel sulfone is the main chemical entity present in sheep blood after monepantel administration and because it is also an active metabolite, its pharmacokinetic properties are of primary importance for the interpretation of future residue and efficacy studies. Overall, these pharmacokinetic data aid in the evaluation of monepantel as an oral anthelmintic in sheep.     

Pharmacokinetic–pharmacodynamic integration of orbifloxacin in rabbits after intravenous, subcutaneous and intramuscular administration

The single-dose disposition kinetics of orbifloxacin were determined in clinically normal rabbits ( n  = 6) after intravenous (i.v.), subcutaneous (s.c.) and intramuscular (i.m.) administration of 5 mg/kg bodyweight. Orbifloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. Minimal inhibitory concentrations ( MIC s) assay of orbifloxacin against 30 strains of Staphylococcus aureus from several European countries was performed in order to compute pharmacodynamic surrogate markers. The concentration–time data were analysed by compartmental and noncompartmental kinetic methods. Steady-state volume of distribution ( V _ss) and total body clearance ( Cl ) of orbifloxacin after i.v. administration were estimated to be 1.71 ± 0.38 L/kg and 0.91 ± 0.20 L/h·kg, respectively. Following s.c. and i.m. administration orbifloxacin achieved maximum plasma concentrations of 2.95 ± 0.82 and 3.24 ± 1.33 mg/L at 0.67 ± 0.20 and 0.65 ± 0.12 h, respectively. The absolute bio-availabilities after s.c. and i.m. routes were 110.67 ± 11.02% and 109.87 ± 8.36%, respectively. Orbifloxacin showed a favourable pharmacokinetic profile in rabbits. However, on account of the low AUC / MIC and C _max/ MIC indices obtained, its use by i.m. and s.c. routes against the S. aureus strains assayed in this study cannot be recommended given the risk of selection of resistant populations.     

Disposition and oral bioavailability of amoxicillin and clavulanic acid in pigs

The pharmacokinetic properties of amoxicillin and clavulanic acid were studied in healthy, fasted pigs after single intravenous (i.v.) and oral (p.o.) dosage of 20 mg/kg of amoxicillin and 5 mg/kg of clavulanic acid. The plasma concentrations of the drugs were determined by validated high-performance liquid chromatographic methods and the pharmacokinetic parameters were calculated by compartmental and noncompartmental analyses. After i.v. administration of the two drugs, plasma concentration-time curves were best described by a three-compartmental open model for amoxicillin and a two-compartmental open model for clavulanic acid. Amoxicillin (with a t(1/2 gamma) = 1.03 h and a clearance of 0.58 L/h.kg) and clavulanic acid (with a t(1/2 beta) of 0.74 h and a clearance of 0.41 L/h.kg) were both rapidly eliminated from plasma. Both drugs had apparently the same volume of distribution of 0.34 L/kg. After p.o. administration of the two drugs, a noncompartmental model was used. Elimination half-lives of amoxicillin and clavulanic acid were not significantly different, i.e. 0.73 and 0.67 h respectively. The mean maximal plasma concentrations of amoxicillin and clavulanic acid were 3.14 and 2.42 mg/L, and these were reached after 1.19 and 0.88 h respectively. The mean p.o. bioavailability was found to be 22.8% for amoxicillin and 44.7% for clavulanic acid.     

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.     

Plasma pharmacokinetics and tissue depletion of cyromazine and its metabolite melamine following oral administration in laying chickens

The study was designed to characterize the plasma pharmacokinetics and tissue depletion profiles (including eggs) of cyromazine (CYR) in chickens following oral administration alone or in combination with melamine (MEL). In order to assess the pharmacokinetic profile of CYR, chickens were administered 1 or 10 mg/kg (single oral doses), whereas residue studies were conducted in chickens fed CYR alone (5 or 10 mg/kg) or CYR (5 mg/kg) and MEL (5 mg/kg) for a period of 14 days. Estimates for the apparent volume of distribution (1.66 L/kg), clearance (7.17 mL/kg/min), and elimination half‐life (2.82 h) were derived by noncompartmental analyses. The highest concentration of CYR occurred in liver but fell below detectable limits within 3 days following drug withdrawal from feed. Combined feeding of MEL with CYR did not significantly alter CYR tissue levels. CYR residues were detected only in egg white and were undetectable at the 2nd day postadministration. No MEL was found in eggs unless it had been added to the feed, and when present, it almost exclusively restricted to the egg white. Based upon the results of this initial study of CYR pharmacokinetics and residue depletion, it appears that use of CYR as a feed additive either alone (5 or 10 mg/kg) or in combination with MEL (both agents at 5 mg/kg) does not produce unsafe residue levels in edible products as long as appropriate withdrawal periods are followed for tissues (3 days) and eggs (2 days). However, our results indicate that adoption of a zero‐day withdrawal period should be reconsidered in light of these results.     

Pharmacokinetics and tissue depletion of florfenicol in Leghorn and Taiwan Native chickens

Chang, S. K., Davis, J. L., Cheng, C. N., Shien, R. H., Hsieh, M. K., Koh, B. W., Chou, C. C. Pharmacokinetics and tissue depletion of florfenicol in Leghorn and Taiwan Native chickens. J. vet. Pharmacol. Therap. 33 , 471–479. Florfenicol (Ff) is a synthetic antibiotic with a broad antibacterial spectrum and high therapeutic effectiveness that was specifically developed for veterinary use. In the present study, tissue residual levels and the pharmacokinetics of Ff after oral administration of 30 mg/kg to Leghorn and Taiwan Native chicken were studied. Furthermore, differential pharmacokinetics between leg and breast muscles were compared using samples collected from an optimized microdialysis model designed for avian species. Significant differences in C_max were detected between the plasma and muscle microdialysates, and between the breast and leg microdialysates of the Leghorn chickens by noncompartmental pharmacokinetic analysis. After a single oral dose of Ff at 30 mg/kg, the drug was quickly absorbed and widely distributed with tissue penetration factors significantly different between leg and breast muscles. The serum protein binding of Ff was estimated to be 16.8 ± 1.2%. Significant breed differences in tissue depletion were noted and characterized by higher Ff concentration in the brain, lung, kidney and at least 12 h longer resident times in kidney, heart and spleen for Taiwan Native chicken. Results from this investigation demonstrate the practicality of using in vivo microdialysis in chickens for pharmacokinetic studies and reveal significant time‐dependent differences in the free concentrations of Ff in leg and breast muscles. The tissue depletion study signified breed differences in tissue residue concentration and detection times between Leghorn and Taiwan Native chickens. Therefore, currently used withdrawal times for Ff in chickens can not be assumed safe for Taiwan Native chickens.     

Comparative pharmacokinetics of intravenous cephalexin in pregnant, lactating, and nonpregnant, nonlactating goats

The aims of this study were to describe and compare the pharmacokinetics of a single dose of cephalexin (10 mg/kg) after its intravenous (i.v.) administration to five goats in three different physiological status: nonpregnant nonlactating (NPNL), pregnant (P) and nonpregnant lactating (L). Blood samples were collected at predetermined times, and plasma concentrations of cephalexin were measured by microbiological assay. Relevant pharmacokinetic parameters were calculated using noncompartmental analysis. Statistical comparison was performed applying the nonparametric anova. No significant differences were found for cephalexin pharmacokinetic parameters between the L and the NPNL group. Median V(dss) was significantly lower in pregnant goats (0.09 [0.07-0.10] L/kg) compared with NPNL goats (0.16 [0.14-0.49] L/kg). Median total Cl and V(dz) were significantly lower in pregnant goats (0.25 [0.19-0.29] L/h·kg and 0.11 [0.10-0.13] L/kg, respectively) than in lactating goats (0.40 [0.32-0.57] L/h·kg and 0.20 [0.14-0.23] L/kg, respectively). Median AUC(0-∞) was significantly higher in pregnant goats (37.79 [34.75-52.10] μg·h/mL) than in lactating goats (25.11 [17.44-31.14] μg·h/mL). Our study showed that even though some pharmacokinetic parameters of cephalexin are altered in pregnant and lactating goats, these differences are unlikely to be of clinical importance; therefore, no dose adjustment would be necessary during pregnancy and lactation.     

Pharmacokinetics of marbofloxacin in freshwater crocodiles (Crocodylus siamensis) after intravenous and intramuscular administration

To evaluate the fate and disposition of marbofloxacin (MBF) in freshwater crocodiles (Crocodylus siamensis), MBF was administered either intravenously (i.v.) or intramuscularly (i.m.) at a dosage of 2.0 mg/kg body weight. The concentrations of MBF in plasma were measured using high‐performance liquid chromatography equipped with a fluorescence detector. The concentrations of MBF in the plasma were measurable up to 144 h after i.v. and i.m. administration. After the first 45 min, the mean pharmacokinetic profiles produced by the two administration routes were almost identical. No statistically significant differences in the pharmacokinetic parameters between the groups were observed. The half‐life was long (about 2.5 days), the volume of distribution was large (about 1.44 L/kg), λz was small (0.01 h^?1), and the clearance was slow (22.6 mL/h/kg). The absolute i.m. bioavailability (F%) was 105.36%. The dose of MBF administered in this study seems to produce appropriate PK‐PD parameters that predict antibacterial success for disease caused by susceptible bacteria. More studies are warranted to evaluate the likely residues after administration of multiple doses.     

Pharmacokinetic characteristics and tissue residues for marbofloxacin and its metabolite N-desmethyl-marbofloxacin in broiler chickens

OBJECTIVES: To determine pharmacokinetic characteristics of marbofloxacin after a single IV and oral administration and tissue residues after serial daily oral administration in chickens. ANIMALS: 40 healthy broiler chickens. PROCEDURE: Two groups of chickens (groups A and B; 8 chickens/group) were administered a single IV and oral administration of marbofloxacin (2 mg/kg). Chickens of group C (n = 24) were given serial daily doses of marbofloxacin (2 mg/kg, PO, q 24 h for 3 days). Plasma (groups A and B) and tissue concentrations (group C) of marbofloxacin and its major metabolite N-desmethyl-marbofloxacin were determined by use of high-performance liquid chromatography. Residues of marbofloxacin and N-desmethylmarbofloxacin were measured in target tissues. RESULTS: Elimination half-life and mean residence time of marbofloxacin in plasma were 5.26 and 4.36 hours after IV administration and 8.69 and 8.55 hours after oral administration, respectively. Maximal plasma concentration was 1.05 microg/ml, and interval from oral administration until maximum concentration was 1.48 hours. Oral bioavailability of marbofloxacin was 56.82%. High concentrations of marbofloxacin and N-desmethyl-marbofloxacin were found in the kidneys, liver, muscles, and skin plus fat 24 hours after the final dose of marbofloxacin; however, marbofloxacin and N-desmethyl-marbofloxacin were detected in only hepatic (27.6 and 98.7 microg/kg, respectively) and renal (39.7 and 69.1 microg/kg, respectively) tissues 72 hours after termination of marbofloxacin treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of pharmacokinetic data obtained in this study reveals that a minimal therapeutic dose of 2 mg/kg, PO, every 24 hours should be appropriate for control of most infections in chickens.     

乳酸恩诺沙星可溶性粉在鸡体内的药动学研究

24只苏禽黄羽肉鸡随机分成2组,分别按10 mg/kg体重剂量静注和内服乳酸恩诺沙星。测定乳酸恩诺沙星在鸡体内的药动学参数和生物利用度。恩诺沙星血药浓度数据用3p87计算机软件处理。静注乳酸恩诺沙星后的血药浓度-时间数据符合二室开放模型,主要动力学参数:t1/2α(0.45±0.16)h,t1/2β(7.02±1.42)h,CL(s)(0.38±0.10)L/kg/h,AUC(23.69±5.56)(mg/L)×h。内服乳酸恩诺沙星的血药浓度时间数据,符合有吸收因素二室模型,主要动力学参数:t1/2ka(0.60±0.01)h,t1/2ke(8.25±1.73)h,tpeak(2.44±0.17)h,Cmax(1.44±0.30)mg/L,AUC(20.74±3.80)(mg/L)×h,F 87.54%。结果表明,乳酸恩诺沙星可溶性粉在鸡体内具有吸收快、分布广、消除较慢以及内服生物利用度高的药动学特征。     

Pharmacokinetics of ofloxacin in broiler chicken

Pharmacokinetics of ofloxacin, a fluoroquinolone antimicrobial agent, was determined in broiler chickens after intravenous or oral administration of a single dose (10 mg/kg). Ofloxacin concentrations in plasma were determined using a high-performance liquid chromatography assay. Plasma concentration profiles were analyzed by the noncompartmental method. Elimination half-life and mean residence time of ofloxacin in plasma were 4.46 and 5.48 h after intravenous administration and 5.85 and 7.43 h, respectively, after oral administration. Maximal plasma concentration of 3.65 microg/mL was achieved at 1.25 h after oral administration. Apparent volume of distribution of 1.76 and 2.16 L/kg and total body clearance of 4.96 and 4.5 mL/min/kg were obtained following intravenous and oral administration, respectively. The oral bioavailability of ofloxacin was 110.01%. Ofloxacin was found to be more rapidly absorbed, widely distributed and more quickly eliminated than other fluoroquinolones in broilers. Based on these kinetic parameters, a dosage of 10 mg/kg given orally every 24 h can be recommended for the treatment of bacterial infections with MIC90 < 0.3 microg/mL.     

Pharmacokinetics of an ampicillin/sulbactam (2:1) combination in rabbits

The pharmacokinetics of a 2:1 ampicillin-sulbactam combination in six rabbits, after intravenous and intramuscular injection at a single dosage of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam) were investigated by using a high performance liquid chromatographic method for determining plasma concentrations. The plasma concentration-time curves were analysed by compartmental pharmacokinetic and noncompartmental methods. The disposition curves for both drugs were best described by an open two-compartment model after intravenous administration and a one-compartment model with first order absorption after intramuscular administration. The apparent volumes of distribution calculated by the area method for ampicillin and sulbactam were 0.62 +/- 0.09 and 0.45 +/- 0.05 L/kg, respectively, and the total body clearances were 0.65 +/- 0.04 and 0.42 +/- 0.05 L/kg h, respectively. The elimination half-lives of ampicillin after intravenous and intramuscular administration were 0.64 +/- 0.11 and 0.63 +/- 0.16 h, respectively, whereas for sulbactam the half-lives were 0.74 +/- 0.12 and 0.77 +/- 0.17 h, respectively. The bioavailability after intramuscular injection was high and similar in both drugs (73.34 +/- 10.08% for ampicillin and 83.20 +/- 7.41% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.20 +/- 0.09 and 0.34 +/- 0.15 h, respectively) and peak concentrations were also similar but nonproportional to the dose of both products administered (13.07 +/- 3.64 mg/L of ampicillin and 8.42 +/- 1.74 mg/L of sulbactam). Both drugs had similar pharmacokinetic behaviour after intramuscular administration in rabbits.     

Bioavailability of amprolium in fasting and nonfasting chickens after intravenous and oral administration

The bioavailability of amprolium (APL) was measured after intravenous (i.v.) and oral (p.o.) administration to chickens. Twelve healthy chickens weighing 1.28–1.41 kg received a dose of 13 mg APL/kg intravenously, and 13 or 26 mg APL/kg orally in both a fasted and a nonfasted condition in a Latin square design. Plasma samples were taken from the subwing vein for determination of APL concentration by HPLC method. The data following intravenous and oral administration were best fitted by 2-compartment and 1-compartment models, respectively, using weighted nonlinear least squares regression. The half-life beta t _½β, volume of distribution ( V d) and total body clearance ( Cl ) after intravenous administration were 0.21 h, 0.12 L/kg and 1.32 L/h.kg, respectively. The elimination half-life ( t _½ K_el) after oral administration was 0.292–0.654 h which is 1.5–3.2 times longer than after intravenous administration, suggesting the presence of a 'flip-flop' phenomenon in chickens. The maximum plasma concentration ( C _max) of 13 mg/kg APL administered orally to chickens during fasting was significantly (about four times) higher than that during nonfasting ( P < 0.05). Bioavailability during nonfasting was from 2.3 to 2.6%, and 6.4% during fasting.     

Platinum pharmacokinetics in sulphur-crested cockatoos (Cacatua galerita) following single-dose cisplatin infusion

OBJECTIVE: To determine the pharmacokinetics of platinum (Pt) in cockatoos. DESIGN: A pharmacokinetic study of Pt, following a single i.v. infusion of cisplatin, was done in six healthy sulphur-crested cockatoos (Cacatua galerita). PROCEDURE: Birds were hydrated for 1 h before and 2 h after a 1-h cisplatin infusion (1 mg/kg, i.v.). Serial blood samples were collected for 96 h after initiation of the infusion and urine was collected for 2 h during the hydration period after cisplatin administration. Tissue samples from 10 organs were obtained at necropsy, 96 h after cisplatin infusion. Total Pt and filterable Pt in plasma, urinary Pt and tissue Pt concentrations were assayed by inductively coupled plasma-mass spectrometry. A noncompartmental pharmacokinetic analysis was performed on the plasma and urine data. RESULTS: For total Pt and filterable Pt, the respective mean systemic clearances were 0.373 and 0.699 L/kg hourly, the steady state volumes of distribution were 4.19 and 0.356 L/kg, and the mean residence times were 111 and 0.512 h. Total plasma Pt displayed a bi-exponential decay profile with average half-lives of 0.398 and 79.0 h, while filterable Pt had a monoexponential decay with mean half-life of 0.413 h. The renal clearance during the 2-h postinfusion period was 0.167 L/kg hourly. The kidneys had the highest Pt accumulation (4.54 micrograms/g DM). CONCLUSIONS AND CLINICAL RELEVANCE: Cisplatin infusion in cockatoos was well tolerated and Pt plasma concentrations were similar to those measured during treatment of solid tumours in human patients. Despite anatomical, physiological and biochemical differences among animal species, the pharmacokinetic disposition of Pt in the cockatoo shares some features with the kinetics reported previously in rodents, dogs and human beings.     

Pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in adult goats

The pharmacokinetic behavior of marbofloxacin was studied in goats after single-dose intravenous (i.v.) and intramuscular (i.m.) administrations of 2 mg/kg bodyweight. Drug concentration in plasma was determined by high performance liquid chromatography (HPLC) and the data collected were subjected to compartmental and noncompartmental kinetic analysis. This compound presented a relatively high volume of distribution (Vss=1.31 L/kg), which suggests good tissue penetration, and a total body clearance (Cl) of 0.23 L/kg small middle doth, which is related to a long elimination half-life (t1/2beta=7.18 h and 6.70 h i.v. and i.m., respectively). Pharmacokinetic parameters were not significantly different between both routes of administration. Marbofloxacin was rapidly absorbed after i.m. administration (Tmax=0.9 h) and had high bioavailability (F=100.74%).     

Disposition of sodium salicylate,flunixin and meloxicam after intravenous administration in broiler chickens

Three nonsteroidal anti-inflammatory drugs (NSAIDs) [sodium salicylate, flunixin (FLU) and meloxicam (MEL)] were administered intravenously to broiler chickens. Plasma concentrations were determined by high-performance liquid chromatography methods and pharmacokinetic parameters were calculated. After intravenous administration of sodium salicylate (50 mg/kg), FLU (1.1 mg/kg) and MEL (0.5 mg/kg), these drugs were eliminated from plasma with a mean half-life of 04.04, 05.45 and 03.20 h, respectively. Apparent volumes of distribution (0.39, 0.08 and 0.12 L/kg, respectively) indicated that tissue distribution was limited for the three drugs. Total body clearance was 70 mL/h.kg for sodium salicylate and 10 and 25 mL/kg.h for FLU and MEL, respectively. Based on the pharmacokinetic parameters these NSAIDs may offer possibilities for treatment of various conditions in chickens.