Pharmacokinetics and oral bioavailability of pentoxyfylline in broiler chickens

The pharmacokinetic properties of pentoxyfylline and its metabolites were determined in healthy chickens after single intravenous and oral dosage of 100 mg/kg pentoxyfylline. Plasma concentrations of pentoxyfylline and its metabolites were determined by a validated high-performance liquid chromatographic method. After intravenous (i.v.) and oral (p.o.) administration, the plasma concentration-time curves were best described by a one-compartment open model. The mean elimination half-life (t(1/2el)) of pentoxyfylline was 1.05 h, total body clearance 1.90 L/h x kg, volume of distribution 2.40 L/kg and the mean residence time was 2.73 h, after i.v. administration. After oral dosing, mean maximal plasma concentration of pentoxyfylline was 4.01 microg/mL and the interval from p.o. administration until maximum concentration was 1.15 h. The mean oral bioavailability was found to be 28.2%. Metabolites I, IV and V were present in chicken plasma after both i.v. and p.o. administration, with metabolite V being the most dominant.     

Pharmacokinetics of azithromycin after i.v. and i.m. administration to sheep

The pharmacokinetics (PK) of azithromycin after i.v. and i.m. injection at a single dosage of 20 mg/kg bodyweight was studied in sheep. Blood samples were collected from the jugular vein until 120 h after dosing for both routes. Plasma concentrations of azithromycin were determined by bioassay. The plasma concentration-time data of azithromycin best fitted a three-compartment model after i.v. administration and a two-compartment model with first-order absorption after i.m. administration. The elimination half-life (t(1/2lambdaz)) was 47.70 +/- 7.49 h after i.v. administration and 61.29 +/- 13.86 h after i.m. administration. Clearance value after i.v. dosing was 0.52 +/- 0.08 L/kg.h. After i.m. administration a peak azithromycin concentration (C(max)) of 1.26 +/- 0.19 mg/L was achieved at 1.24 +/- 0.31 h (t(max)). Area under the curve (AUC) were 38.85 +/- 5.83 mg.h/L and 36.03 +/- 1.52 mg.h/L after i.v. and i.m. administration respectively. Bioavailability obtained after i.m. administration was 94.08 +/- 11.56%. The high tolerability of this i.m. preparation and the favourable PK behaviour such as the long half-life and high bioavailability make azithromycin likely to be effective in sheep.     

Pharmacokinetics and oral bioavailability of sulfadiazine and trimethoprim in broiler chickens

Sulfonamides and trimethoprim are chemotherapeutics that are extensively used in various animal species. Little information about the pharmacokinetics of these compounds in chickens exists in the literature. In this study, a new commercial formulation of sulfadiazine in combination with trimethoprim was administered both intravenously and orally, according to a crossover design, to healthy, 7-week-old broilers. The plasma concentrations of the drugs were determined by validated high-performance liquid chromatographic methods, and pharmacokinetic parameters were calculated. After intravenous or oral administration of trimethoprim (6.67 mg/kg body weight) and sulfadiazine (33.34 mg/kg body weight), both active substances were rapidly eliminated from the plasma. There was a mean half-life of 1.61 h for trimethoprim and 3.2 h for sulfadiazine. The apparent volumes of distribution (2.2 and 0.43 L/kg, respectively, indicated that the tissue distribution of trimethoprim was more extensive than that of sulfadiazine. The oral bioavailability was approximately 80% for both components.     

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.     

Pharmacokinetics of gatifloxacin in broiler chickens following intravenous and oral administration

1. The pharmacokinetics of gatifloxacin were investigated following intravenous and oral administration of a single dose at a rate of 10?mg/kg body weight in broiler chicks.

2. Drug concentration in plasma was determined using High Performance Liquid Chromatography with ultraviolet detection on samples collected at frequent intervals after drug administration.

3. Following intravenous administration, the drug was rapidly distributed (t_1/2α: 0·33?±?0·008?h) and eliminated (t_1/2β: 3·62?±?0·03?h; Cl_B: 0·48?±?0·002?l/h/kg) from the body.

4. After oral administration, the drug was rapidly absorbed (C _max: 1·74?±?0·024?µg/mL; T _max: 2?h) and slowly eliminated (t_1/2β: 3·81?±?0·07?h) from the body. The apparent volume of distribution (V_d(area)), total body clearance (Cl_B) and mean residence time (MRT) were 3·61?±?0·04?l/kg, 0·66?±?0·01?l/h/kg and 7·16?±?0·08?h, respectively. The oral bioavailability of gatifloxacin was 72·96?±?1·10 %.

5. Oral administration of gatifloxacin at 10?mg/kg is likely to be highly efficacious against susceptible bacteria in broiler chickens.     

Pharmacokinetics of ketamine HC1 and metabolite I in the cat: a comparison of i.v., i.m., and rectal administration

Ketamine HCl [2-(o-chlorophenyl)-2-(methylamino) cyclohexanone HCl] concentrations in whole blood were used to study the pharmacokinetics of i.v., i.m., and rectal administrations, at a dose of 25 mg/kg, in normal domestic cats. Absorption was rapid with both the i.m. and rectal routes. Systemic availability was 51% (SEM 10) for the i.m. dose and 43.5% (SEM 6.1) for the rectal dose. The first-pass effect had a minimal influence on the metabolism of ketamine HCl administered rectally. The elimination rate constant (beta) of the drug was statistically similar in the i.v., i.m., and rectal groups, at a 95% level of significance (P less than 0.05). At the dosage rates studied, ketamine HCl produced an anesthetic effect in the cat following i.v., i.m. and rectal administration.     

Pharmacokinetics and tissue fluid distribution of cephalexin in the horse after oral and i.v. administration

The purpose of this study was to determine the pharmacokinetics and tissue fluid distribution of cephalexin in the adult horse following oral and i.v. administration. Cephalexin hydrate (10 mg/kg) was administered to horses i.v. and plasma samples were collected. Following a washout period, cephalexin (30 mg/kg) was administered intragastrically. Plasma, interstitial fluid (ISF) aqueous humor, and urine samples were collected. All samples were analyzed by high-pressure liquid chromatography (HPLC). Following i.v. administration, cephalexin had a plasma half-life (t(1/2)) of 2.02 h and volume of distribution [V(d(ss))] of 0.25 L/kg. Following oral administration, the average maximum plasma concentration (C(max)) was 3.47 mug/mL and an apparent half-life (t(1/2)) of 1.64 h. Bioavailability was approximately 5.0%. The AUC(ISF):AUC(plasma) ratio was 80.55% which corresponded to the percentage protein-unbound drug in the plasma (77.07%). The t(1/2) in the ISF was 2.49 h. Cephalexin was not detected in the aqueous humor. The octanol:water partition coefficient was 0.076 +/- 0.025. Cephalexin was concentrated in the urine with an average concentration of 47.59 microg/mL. No adverse events were noted during this study. This study showed that cephalexin at a dose of 30 mg/kg administered orally at 8 h dosage intervals in horses can produce plasma and interstitial fluid drug concentrations that are in a range recommended to treat susceptible gram-positive bacteria (MIC < or = 0.5 microg/mL). Because of the low oral bioavailability of cephalexin in the horse, the effect of chronic dosing on the normal intestinal bacterial flora requires further investigation.     

The oral bioavailability of ibuprofen enantiomers in broiler chickens

Doses of racemic ibuprofen ranging from 5 to 20 mg/kg body weight were administered intravenously (i.v.) and orally to broiler chickens and plasma concentration-time profiles for both ibuprofen enantiomers were determined. The absorption of ibuprofen was evaluated after a bolus administration of a commercially available suspension into the crop and proventriculus, respectively. An enterohepatic circulation as described for other nonsteroidal anti-inflammatory drugs (NSAIDs) in other species could be suggested for both enantiomers after i.v. and oral administration. Significantly higher area under the curve (AUC) values for S(+)-ibuprofen compared with R(-)-ibuprofen were collected after crop and proventriculus administration. Several factors could be responsible for the significant differences in AUC values between both enantiomers.     

Pharmacokinetics of azithromycin in foals after i.v. and oral dose and disposition into phagocytes

The properties of azithromycin suggest that it may be an alternative to erythromycin for treatment of Rhodococcus equi pneumonia in foals. To investigate this possibility, the disposition of azithromycin in plasma, polymorphonuclear leukocytes (PMN), and alveolar cells was examined after a single administration in foals. Azithromycin suspension was administered orally (p.o.) at a dose of 10 mg/kg to five healthy 2-3-month-old foals. Two weeks later, azithromycin for injection was administered by intravenous (i.v.) infusion at a dose of 5 mg/kg to the same foals. Plasma samples were collected after p.o. and i.v. administration. Peripheral blood PMN and bronchoalveolar lavage fluid and alveolar cells were collected after p.o. administration. Azithromycin concentrations were determined by reverse-phase high-performance liquid chromatography (HPLC) with coulometric electrochemical detection. Azithromycin p.o. absorption was variable with a mean systemic availability of 39% (+/-20%). The plasma half-life was 16 and 18.3 h after i.v. and p.o. administration, respectively. Azithromycin had a very large volume of distribution (V(d)) of 11.6 L/kg [V(d(ss))] and 12.4 L/kg [V(d(area))]. The large V(d) can be attributed to high tissue and intracellular concentrations, exhibited by the high concentration of azithromycin in PMN and alveolar cells. The PMN half-life was 49.2 h. Dosage of 10 mg/kg of azithromycin p.o. once daily for foals with R. equi pneumonia is recommended for further study.     

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

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

Disposition of norfloxacin in broiler chickens and turkeys after different methods of oral administration

Norfloxacin was administered orally to chickens and turkeys at 15 mg/kg body weight by pulse dosing at 24 h intervals and by continuous dosing at 100 mg/L in drinking water for five days. Blood samples were taken serially. Plasma norfloxacin concentrations were determined by high-performance liquid chromatography. The plasma norfloxacin concentrations increased slowly during continuous dosing and reached the MIC(90) (250 ng/mL) for Gram-negative pathogens by 12 h in chickens and 18 h in turkeys. The steady-state plasma concentration was attained in 36 h and remained at approximately 776.67+/-33.23 ng/mL in chickens and 682.50+/-28.55 ng/mL in turkeys. After pulse dosing, the plasma norfloxacin concentrations increased rapidly and exceeded the MIC(90) at 2 h in both species and remained above MIC(90) for 8 h in chickens and 6 h in turkeys. Pulse dosing provided half the steady-state concentration that was achieved by continuous dosing, 365.32+/-39.31 ng/mL in chickens and 306.03+/-32.26 ng/mL in turkeys, during the dosing interval of 24 h. Data for daily pulse dosing suggested that every administration corresponded to a single, daily repeated bolus administration although pulse dosing produced higher plasma concentrations more readily. Continuous and pulse dosing are both rational for the administration of norfloxacin to flocks of chickens and turkeys. We recommend that treatment be commenced with a pulse oral dose administered over a 4 h period and maintained by continuous oral medication for three to five consecutive days.     

Pharmacokinetics and i.m. bioavailability of ceftiofur in Asian elephants (Elephas maximus)

Captive elephants are prone to infections of the feet, lungs, and skin. Often treatment regimens are established with no pharmacokinetic data on the agents being used for treatment in these species. A pharmacokinetic study using ceftiofur (1.1 mg/kg) was conducted in four adult female captive Asian elephants (Elephas maximus) at Busch Gardens in Tampa, Florida. Elephants were given both i.v. and i.m. administrations in a complete crossover design with a 3-week washout period between treatments. Blood samples were collected prior to drug administration and at 0.33, 0.67, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 h postadministration. Ceftiofur analysis was performed using a validated liquid chromatography/mass spectrophotometric (LC/MS) assay. Plasma concentrations for the i.m. samples were lower than expected. The mean C(max) following i.m. administration was 1.63 microg/mL with a corresponding T(max) of 0.55 h. Following i.v. administration, the median V(d(ss)) was 0.51 L/kg and a median Cl(p) of 0.069 L/kg/h. Mean i.m. bioavailability was 19%. The results indicate that ceftiofur used at 1.1 mg/kg i.m. could be useful in elephants when given two to three times a day or alternatively, 1.1 mg/kg i.v. once daily, depending upon the MIC of the pathogen.     

Pharmacokinetics of tylosin in broiler chickens

Biological availability and pharmacokinetic properties of tylosin were determined in broiler chickens after oral (p.o.) and intravenous (i.v.) administration at a dose of 10 mg/kg. The calculated bioavailability--F%, by comparing AUC values--p.o. and AUC--i.v., ranged from 30%-34%. After intravenous injection tylosin was rapidly distributed in the organism, showing elimination half-life (t1/2 beta) values of 0.52 h and distribution volume (Vd) of 0.69 L/kg, at a clearance rate (Cl) of 5.30 +/- 0.59 ml/min/kg. After oral administration, tylosin has a similar distribution volume (Vd = 0.85 L/kg), while the elimination half-life t1/2 beta of 2.07 h was four times bigger than after i.v. administration at Cl = 4.40 +/- 0.27 ml/min/kg. The obtained value tmax = 1.5 h for tylosin after oral administration indicates that using this antibiotic with drinking water in broiler chickens is the method of choice. However, a relatively low value Cmax = 1.2 micrograms/ml after oral administration of tylosin shows that dosing of this antibiotic in broiler chickens should be higher than in other food producing animals.     

Pharmacokinetics of butorphanol in broiler chickens

Butorphanol tartrate (2 mg/kg) was injected intravenously in 18 healthy broiler chickens to study its pharmacokinetics. Plasma samples were analysed by a highly sensitive high-performance liquid chromatography with diode-array detection method and pharmacokinetic parameters were calculated from the mean pooled data. With non-compartmental analysis, the terminal half-life (T(1/2.z)) was 71.3 minutes, clearance was 67.6 ml/minute/kg and the apparent volume of distribution was 6.9 l/kg. The concentration-time curve was also fitted to a two-compartmental model. In this analysis, elimination half-life (T(1/2β)) was 69.3 minutes, clearance was 74.6 ml/minute/kg and volume of distribution at steady state was 5.6 l/kg. The micro rate constants k(21), k(12) and k(10) were 0.034, 0.050 and 0.029, respectively. Butorphanol was well distributed in the chickens with rapid clearance. It remained above the minimum effective concentration for analgesia in mammals for approximately two hours in the chickens.     

Pharmacokinetics of valnemulin after intravenous,intramuscular, and oral administration in layer chickens

The pharmacokinetic characteristics of valnemulin in layer chickens were studied after single intravenous, intramuscular, and oral administration at a dose of 15 mg/kg body weight. Plasma samples at certain time points were collected and the drug concentrations in them by ultra high‐performance liquid chromatography tandem mass spectrometry (UHPLC‐MS). The concentration–time data for each individual were plotted by noncompartmental analysis for the whole three routes. Following intravenous administration, the plasma concentration showed tiny fluctuation. The elimination half‐life (), total body clearance (Cl), and area under the plasma concentration–time curve (AUC) were 1.85 ± 0.43 h, 2.2 ± 0.9 L/h, and 7.52 ± 2.46 μg·h/mL, respectively. Following intramuscular administration, the peak concentration (C_max, 1.40 ± 0.43 μg/mL) was achieved at the time of 0.34 h. A multiple‐peak phenomenon existed after oral administration, and the first peak and secondary peak were at 10 min and during 2–4 h, respectively, while the tertiary peak appeared during 5–15 h. The bioavailability (F %) for intramuscular and oral administration was 68.60% and 52.64%, respectively. In present study, the detailed pharmacokinetic profiles showed that this drug is widely distributed and rapidly eliminated, however has a low bioavailability, indicating that valnemulin is likely to be a favorable choice in the clinical practice.