Bioavailability and pharmacokinetics of phenylbutazone in the cow

Phenylbutazone was administered orally and intravenously at a dose of 5 mg/kg to healthy cows and to cows positive for bovine leukaemia virus (BLV). Pharmacokinetic parameters and bioavailability were investigated. No differences were seen in the parameters between the healthy and BLV positive animals. The biological half-lives ranged from 31.4 to 82.1 h after intravenous administration and from 38.6 to 78.2 h after oral administration. The mean value of the apparent volume of distribution was 0.09 litres/kg. Total body clearance ranged from 0.78 to 1.94 ml/kg/h. The average systemic availability was 67.5% with a wide variation among the animals (range 41.9–95.5%). Based on the disposition kinetics and on the therapeutic concentration range suggested in man, an oral loading dose ranging from 10 to 20 mg/kg and a daily maintenance dose ranging from 2.5 to 5 mg/kg can be proposed.     

Bioavailability and pharmacokinetics of florfenicol in broiler chickens

The bioavailability and pharmacokinetic disposition of florfenicol in broiler chickens were investigated after intravenous (i.v.), intramuscular (i.m.) and oral administrations of 15 and 30 mg/kg body weight (b.w.). Plasma concentrations of florfenicol were determined by a high performance liquid chromatographic method in which plasma samples were spiked with chloramphenicol as internal standard. Plasma concentration-time data after i.v. administration were best described by a two-compartment open model. The elimination half-lives were 168 +/- 43 and 181 +/- 71 min, total body clearance 1.02 +/- 0.17 and 1.02 +/- 0.16 L x kg/h, the volume of distribution at steady-state 4.99 +/- 1.11 and 3.50 +/- 1.01 L/kg after i.v. injections of 15 and 30 mg/kg b.w., respectively. Plasma concentration-time data after i.m. and oral administrations were adequately described by a one-compartment model. The i.m. bioavailability and the oral bioavailability of florfenicol were 95, 98 and 96, 94%, respectively, indicating that florfenicol was almost absorbed completely after i.m. and oral administrations of 15 and 30 mg/kg b.w.     

Bioavailability and pharmacokinetics of sulfamethazine in the pony

Sulfamethazine has been used in therapy of equine disease for over 40 years (Welsh et al , 1946). Although sulfamethazine appears to be well absorbed when fed mixed with grain and is reported to reach its peak concentration 8 h after administration, its oral bioavailability and pharmacokinetics have not been reported (Schroeder et al. , 1948; Meier et al , 1980). The purpose of the present study was to determine the major pharmacokinetic values and the oral bioavailability of sulfamethazine at a dosage predicted to produce therapeutic blood concentrations in the pony.     

Bioavailability and pharmacokinetics of florfenicol in healthy sheep

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

Bioavailability and pharmacokinetics of ibuprofen in the broiler chicken

The intravenous, intramuscular and oral pharmacokinetics of ibuprofen in broiler chickens were investigated. In a preliminary study, plasma ibuprofen concentration-time profiles, following i.v. (25 mg/kg) dosing were best described by a 2-compartment model. After intravenous administration, the volume of distribution at steady-state ( V _d(ss)), the total systemic clearance ( Cl _B), the elimination half-life (t_1/2p) and the MRT were 0.303 L/kg, 482.3 ml/h-kg, 2.71 h and 1.02 h, respectively. After intramuscular administration of ibuprofen, the t _max and C _max were 0.37 h, and 42.2μg/mL, respectively, with an estimated bioavailability of 46.7%. After oral administration of ibuprofen, the t _max and C _max were 0.31 h and 23.91 μg/mL, respectively, with an estimated bioavailability of 24.2%. This is a preliminary study, examining the use of ibuprofen in broiler chickens, and should be followed by tissue residue and efficacy studies in different disease states.     

Bioavailability and pharmacokinetics of metronidazole in fed and fasted horses

Britzi, M., Gross, M., Lavy, E., Soback, S., Steinman, A. Bioavailability and pharmacokinetics of metronidazole in fed and fasted horses. J. vet. Pharmacol. Therap. 33 , 511–514. Metronidazole (1‐[2‐hydroxyethyl]‐2‐methyl‐5‐nitroimidazole) is a bactericidal antimicrobial agent used for treatment of infectious diseases caused by anaerobic bacteria and protozoa. Pharmacokinetics of metronidazole following its administration to horses was previously described ( Sweeney et al., 1986 ; Baggot et al., 1988 ; Specht et al., 1992 ; Steinman et al., 2000 ). The bioavailability (F) was 85% (ranging from 57% to 105%) and the time to reach maximum serum concentration (t_max) was 1–2 h after oral dose at 25 mg/kg body weight ( Sweeney et al., 1986 ). Baggot et al. (1988) found that F was 74.5% (ranging from 58.4% to 91.5%) and t_max was 1.5 h after oral dose at 20 mg/kg body weight. Specht et al. (1992) reported that F was 97% (ranging from 79% to 111%) and t_max was 40 min after oral dose at 15 mg/kg body weight. In an earlier study by our group F was 74% and t_max was 65 min after oral dose at 20 mg/kg body weight ( Steinman et al., 2000 ). These individual variations in F might be partially explained by the effect of feed, among other factors, mainly on metronidazole absorption. Interactions between food and drugs may reduce or increase the drug effect. The majority of clinically relevant food–drug interactions are caused by food‐induced changes on the bioavailability of the drug ( Schmidt & Dalhoff, 2002 ). In dogs, absorption of metronidazole is enhanced when given with food, but delayed in humans ( Plumb, 1995 ). Although, metronidazole is used commonly to treat various clinical conditions in horses with relatively little adverse effects ( Sweeney et al., 1991 ), narrow margin of safety was suggested because histological evidence of peripheral neurotoxicity and hepatotoxicity were noted in horses treated with doses as low as 30 mg/kg body weight every 12 h orally for 30 days ( White et al., 1996 ). For drugs with a narrow therapeutic index, even small changes in dose–response effects can have significant consequences ( Schmidt & Dalhoff, 2002 ).     

Bioavailability of vitamin A sources for cattle

An experiment was conducted to evaluate the bioavailability of 5 sources of vitamin A. It was hypothesized that some vitamin A products have protective coatings that are more resistant than others to rumen destruction and that such protection would result in greater tissue concentrations of vitamin A. Fifty-three yearling Angus x Brahman cattle, consisting of 39 steers and 14 heifers, were stratified by BW and sex and randomly assigned to 6 high-concentrate diet groups receiving no vitamin A supplementation (control) or vitamin A supplemented from the following sources: Microvit A (Adisseo, Acworth, GA), Rovamix A (DSM, Parsippany, NJ), Sunvit A, Lutavit A, and Microvit A DLC (Adisseo). The vitamin A treatment groups were fed daily 80,000 IU of retinol/animal in a low-retinol concentrate diet (78.5% oats, 10% cottonseed hulls, 8% molasses, and 2% cottonseed meal; DM basis) and a free-choice, poor quality (low carotene) hay for 84 d. Every 28 d, BW was determined and liver biopsies and plasma were collected and analyzed for retinol concentrations. All retinol treatments showed significant increases in liver retinol concentrations compared with control animals (P < 0.0001), which steadily decreased over time. At all collection times, Microvit A led to numerically, but not significantly, greater concentrations of retinol in liver than did all other treatments. However, at the end of the experiment, there was no significant difference in liver retinol concentration among Microvit A, Rovamix A, Lutavit A, and Microvit A DLC diets. When liver retinol concentrations at all collection times were considered, Microvit A and Rovamix A appeared to provide the most bioavailable vitamin A.     

The pharmacokinetics of fenbendazole and oxfendazole in cattle

The pharmacokinetics of fenbendazole and oxfendazole in cattle are described. The pharmacokinetics of oxfendazole were not significantly different when administered orally and by intra-ruminal injection. At a dose rate of 4.5 mg/kg, administered orally, fenbendazole gave rise to mean peak concentrations in plasma of fenbendazole and oxfendazole of 0.11 and 0.13 g/ml respectively. Oral administration of oxfendazole, at 4.5 mg/kg body weight, gave rise to plasma peak concentrations of fenbendazole and oxfendazole of 0.10 and 0.20 g/ml respectively. Following intra-ruminal administration of oxfendazole, the peak concentrations were 0.11 and 0.18 g/ml respectively.     

Thiamphenicol pharmacokinetics in beef and dairy cattle

The pharmacokinetics of thiamphenicol were investigated in 10 calves and six lactating cows. It was found that this drug is rapidly absorbed (1 5 min) following intramuscular injection with an absorption rate constant and a bioavailability of 8.7 h^-1 and 84%, respectively. The drug appears to be widely distributed into various body fluids, yielding a volume of distribution (V_d(area)) of approximately 0.9 l/kg. The micro-rate constants indicated that the antibiotic rapidly diffuses into the peripheral compartment (k₁₂ > k₂₁). Elimination from plasma is relatively rapid, with a biological half-life of about 1.75 h. Thiamphenicol appears shortly in milk (15 min) after its intravenous administration, and gives milk to plasma concentration ratios greater than one between 4 and 12 h.     

Bioavailability,pharmacokinetics and residues of chloramphenicol in the chicken*

Anadón, A., Bringas, P., Martinez-Larrañaga, M.R., Diaz, M.J. Bioavailability, pharmacokinetics and residues of chloramphenicol in the chicken. J. vet. Pharmacol Therap. 17 , 52–58. The pharmacokinetic properties of chloramphenicol were determined in broiler chickens after two sinSle oral doses (30 and 50 mg/kS body weight) and after a single intravenous (i.v.) dose (30 mg/kg body weight). After oral and i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. After oral administration (30 and 50 mg/kg). chloramphenicol was absorbed rapidly (time to maximal concentration of 0.72 or 0.60 h) and eliminated with a mean half-life (t_½β) of 6.8 7 or 7.41 h, respectively. The bioavailability was 29% at 30 mg/kg chloramphenicol and 38% at 50 mg/kg chloramphenicol. Concentrations greater than 5 (m̈g/ml were achieved at 15 min and persisted up to 2 or 4 h post-administration, respectively. Statistically significant differences between the two routes of administration were found for the pharmacokinetic variables, half-lives of both distribution and elimination phases (t_½αt_½β) and apparent volume of distribution [V_d(area)]. The mean t_½β of chloramphenicol and i.v. administration was 5.23 h. Chloramphenicol was extensively metabolized into dehydrochloramphenicol (DH-CAP), nitrophenylaminopropanedione (NPAP) and nitroso-chlorampheni-col (NO-CAP) derivatives. Residues of chloramphenicol (CAP) and the three metabolites DH-CAP, NPAP and NO-CAP in kidney, liver and muscle were measured in chickens that received an oral dose of 50 mg/kg once daily for 4 days. The results indicate that CAP and DH-CAP residues were cleared slowly and were at or below the detection limit of 0.005 m̈g/ml within 12 days after dosing. However, at the time of slaughter (12 days), the NPAP and NO-CAP residues were detected in the tissue.     

Comparative pharmacokinetics of fenbendazole in buffalo and cattle

Swamp buffalo (Bubalus bubalis) and Droughtmaster cattle (Bos indicus × B. taurus), fitted with gastrointestinal cannulae, were dosed intraruminally with fenbendazole at 7.5 mg/kg liveweight, together with a chromium oxide capsule and a pulse dose of NaCoEDTA, to estimate the flow dynamics of the digesta in the rumen and duodenum. The concentrations of fenbendazole (FBZ) metabolites were measured in plasma and duodenal fluid collected over 120 h. In plasma, significantly lower peak concentrations and earlier disappearance of FBZ and its sulphoxide (OFZ) metabolite were observed in buffalo, which considerably reduced systemic availability in comparison with cattle. The availability of OFZ in the duodenal fluid of buffalo was significantly lower, whereas FBZ disposition was similar to that in cattle. The turnover rate of fluid in the rumen was higher in buffalo than in cattle, while the flow parameters for other digesta were similar in the two species. It is concluded that the decreased absorption of drug in buffalo was attributable to the shorter residence time of the dose in the rumen, and probably in the entire gastrointestinal tract. This may reduce the efficacy of treatment and indicate the need for higher dose rates for benzimidazole anthelmintics in buffalo than in cattle.Abbreviations AAS atomic absorption spectroscopy - AUC area under the concentration-versus-time curve - C _max maximum concentration - FBZ fenbendazole - FBZ.SO₂ fenbendazole sulphone - HPLC high-performance liquid chromatography - OFZ fenbendazole sulphoxide     

The pharmacokinetics of fenbendazole and oxfendazole in cattle

The pharmacokinetics of fenbendazole and oxfendazole in cattle are described. The pharmacokinetics of oxfendazole were not significantly different when administered orally and by intra-ruminal injection. At a dose rate of 4.5 mg/kg, administered orally, fenbendazole gave rise to mean peak concentrations in plasma of fenbendazole and oxfendazole of 0.11 and 0.13 microgram/ml respectively. Oral administration of oxfendazole, at 4.5 mg/kg body weight, gave rise to plasma peak concentrations of fenbendazole and oxfendazole of 0.10 and 0.20 microgram/ml respectively. Following intra-ruminal administration of oxfendazole, the peak concentrations were 0.11 and 0.18 microgram/ml respectively.     

Bioavailability, pharmacokinetics, and tissue distribution of 14C homidium after parenteral administration to Boran cattle

The absorption, distribution and elimination characteristics of ¹⁴C homidium have been described in non-infected and Trypanosoma congolense -infected cattle treated with ¹⁴C homidium chloride by either intramuscular (i.m.) or intravenous (i.v.) injection at a dose level of 1 mg/kg body weight. Results show that the mean (± SD) elimination of the drug from plasma followed a biexponential process, with half-lives of 0.084 ± 0.006 h and 97.66 ± 16.28 h for the distribution and elimination phases after intravenous injection, respectively. Bioavailability of the intramuscular dose was 62.5% and 57.8% in non-infected and trypanosome-infected cattle, respectively. Absorption was rapid, with a t _max of 15 min and a mean C _max (± SD) of 268.4 ± 4.09 ng/mL following the intramuscular dose in non-infected cattle. The major route of excretion was via faeces. Approximately 90% of the total dose given to non-infected i.m.-treated cattle was excreted within 14 days. Following intramuscular administration of the drug, residues remained high in the major excretory organs, with the liver having concentrations of 1411 and 1199 ng/g after 14 and 28 days, respectively. Over the same period, the values in the kidneys were 649 and 448 ng/g. Concentrations in the liver 14 and 21 days following i.v. treatment were 2195 and 2454 ng/g, respectively. These results show that there was no significant difference in liver drug residues between 14 and 21 days, or 28 days depending on the treatment given, suggesting that once the drug is in this organ, it is released back into the circulation at an extremely slow rate.     

Clinical pharmacokinetics of parenterally administered danofloxacin in cattle

Danofloxacin is a new fluoroquinolone antibacterial, developed specifically for veterinary use. Its in vitro activity and pharmacokinetic properties have been investigated to assess its potential for use in the therapy of respiratory disease in cattle. The minimum inhibitory concentration of danofloxacin against 90% (MIC90) of contemporary European and North American field isolates of Pasteurella haemolytica, Pasteurella multocida and Haemophilus somnus, the most important bacterial respiratory pathogens of cattle, was 0.125 micrograms/ml. The plasma and lung kinetics of danofloxacin following parenteral administration of 1.25 mg/kg were evaluated in two studies. Danofloxacin was rapidly absorbed following intramuscular and subcutaneous injection and bioavailability was virtually complete (101% and 94% respectively). Plasma concentration profiles of danofloxacin were similar for intramuscular and subcutaneous routes with no significant differences in the area under the plasma concentration-time curves (AUC) following one, three or five consecutive daily doses, although slightly higher peak plasma concentrations were achieved by the intramuscular route. Following intramuscular administration, the mean peak lung concentration of danofloxacin was 4.1 times greater than that of plasma. Similarly, the AUC for lung tissue was 3.7 times greater than that for plasma. These data indicate that danofloxacin should be particularly appropriate for the therapy of bacterial respiratory disease in cattle.     

Comparative pharmacokinetics of febantel and its metabolites in sheep and cattle

The pharmacokinetics of febantel and its main metabolites were studied in cattle and sheep. Seven ewes and 4 heifers were given febantel orally in a single dose of 7.5 mg/kg, 25 mg/kg, or 45 mg/kg of body weight. Plasma concentrations vs time of febantel and individual metabolites were determined by high-performance liquid chromatography analysis. Intestinal absorption of febantel was faster and biotransformations were more active in sheep than in cattle.     

The effect of sex and age on caffeine pharmacokinetics in cattle

The aim of this study was to determine the effect of sex on the pharmacokinetics of caffeine in cattle at different ages. Ten female and 10 male Holstein cattle were subject to a caffeine test when they were aged 1, 2, 4, 6, 8, 12 and 18 months. Caffeine, 5 mg kg(-1)body weight, was given intravenously as a sterile isotonic solution. An automated, enzyme-multiplied, immunoassay technique (EMIT) was used to determine plasma caffeine concentration. The volume of distribution of caffeine (V(SS)) decreased significantly between 1 and 18 months of life. Mean V(SS)values observed in males and females were not statistically different. The experimental period was characterised by a steady decrease (statistically significant) in caffeine mean residence time (MRT). These values did not differ significantly between males and females under 8 months of age. In 8-, 12- and 18-month-old animals, the caffeine MRT in the females was significantly shorter than in the males. The total plasma clearance (Cl(tot)) of caffeine increased significantly between 1 and 18 months of age. No significant differences were observed between total plasma clearance of caffeine in males and females under 8 months of age. In 8-, 12- and 18-month-old animals, the Cl(tot)of caffeine was significantly higher in females than in males. In conclusion, we report a sex-linked difference in pharmacokinetics of caffeine in cattle over 8 months of age, the females being the more active metabolisers. The results of the present study support the hypothesis that the metabolism of xenobiotics is sexually different in ruminants.     

Bioavailability of magnesium in beef cattle fed magnesium oxide or magnesium hydroxide

Two experiments were conducted to compare Mg bioavailability from Mg oxide (MgO) vs Mg hydroxide (Mg(OH)2) fed in either a completely mixed diet or a mineral supplement. In Exp. 1, these Mg sources were incorporated into completely mixed diets and offered to 15 steers (282 kg) allotted to three treatments: control diet containing .19% Mg, control plus .2% added Mg as MgO, or control plus .2% added Mg as Mg(OH)2. Each calf was fed 5 kg/d of the respective diet during 10-d adjustment and 7-d collection periods. Blood samples were collected on d 1, 3 and 7. Mg supplementation increased (P less than .01) fecal and urinary Mg excretions, whereas apparent Mg absorption (%) and retention were similar (P greater than .10) for all treatments. Plasma Mg concentrations were similar (P less than .10) for calves supplemented with MgO and Mg(OH)2 but were higher (P less than .05) for Mg supplemented than for control calves on d 7. In Exp. 2, these Mg sources were incorporated into mineral supplements and offered free choice to 30 spring-calving beef cows gazing tetany-inducing pastures from March 6 to May 1. Each of three groups of 10 cows was assigned to a 5.7-ha tall fescue pasture and offered either a control supplement or a supplement containing 40% MgO or Mg(OH)2. Blood samplers were collected on d 0, 7, 14, 28, 42 and 56. Plasma Mg concentrations were not different (P greater than .10) for cows offered MgO and Mg(OH)2 but were higher (P less than .01) for Mg-supplemented than for control cows on d 28, 42 and 56.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacodynamics, pharmacokinetics and faecal persistence of morantel in cattle and goats

Morantel could not be detected (<0.05 pg/ml)in the plasma of cattle or goats followingthe oral administration of morantel tartrate at a dose rate of 10 mg/kg
bodyweight. No morantel was detected in the milk of lactating goats except in
one animal where a concentration of 0.092 pg/ml was detected at 8 h after drug
administration. Morantel was highly effective against Cooperia oncophora infec-
tions in calves treated 6, 9 or 18 days after infection; however, was highly
effective against Ostertagia ostertagi only when treated 18 days after infection.
Morantel did not affect the fecundity of adult 0.ostertagi surviving treatment 18
days after infection which had similar average numbers of eggs in their uteri
(range 13.4 f 0.73-16.8 L 0.98) as did parasites from control animals (range
12.0 k 0.70-13.6 2 0.66). Morantel could be detected at a concentration of 96 k
4.5 pgig (dry weight) in the faeces of a calf 24 h after treatment with I0 mgikg
bodyweight of morantel tartrate. The concentration of morantel in replicate
samples of this faeces exposed to natural atmosphere, but not to soil or soil
organisms, declined slowly over the following 322 days. At day 322 after the start
of the experiment 8.8 pg/g of morantel could be measured in the remaining
faecal material. Throughout the faecal degradation study the concentration of
morantel in the crusts of the replicate sample pats was lower than the
concentration in the core samples.