Comparison of pharmacokinetic parameters for two oxytetracycline preparations in pigs

Pharmacokinetics of oxytetracycline (OTC) were studied in 10 pigs after administration of 20 mg/kg body weight of either a conventional (OTC-C) or a long-acting (OTC-LA) preparation.
After intravenous administration of OTC-C the elimination half-life for OTC was 3.75 h, with approximately 75% of the dose being excreted in the urine in 1 week. Intramuscular (i.m.) injection of OTC-C resulted in plasma peak values after 4 h, while OTC-LA after i.m. administration produced the highest plasma levels within 1 h, although these were lower than with OTC-C.
For both preparations the bioavailability after i.m. administration was 95–100% and about 70% of the dose was excreted in the urine during the first week.
With OTC-C given i.m., plasma concentrations above 0.5 μg/ml were maintained for 28 h and with OTC-LA for 35 h indicating a weak retard effect of the latter.
Pronounced tissue damage at the injection site was seen 1 and 2 weeks after the administration of OTC-LA, while OTC-C produced very little irritation. OTC could be found at the injection site for 2 weeks, the concentrations being higher for OTC-LA than for OTC-C.     

A comparison of the oxytetracycline preparations Aquacycline and Terramycin 100 with regard to absorption characteristics, local tissue reactions and residues following dewlap injections in calves

In an experiment with 12 calves, Aquacycline® in a 5 % (OTC-A5) and a 10 % (OTC-A10) solution, was compared with Terramycin®-100 (OTC-C) by injecting 20 mg OTC/kg bwt. of these preparations in the dewlap and monitoring serum concentrations as well as tissue reactions and residues at the site of injection. All 3 preparations resulted in oxytetracycline (OTC) serum concentrations above 0.5 µg/ml of approximately 60 h. During this period, OTC-A5 resulted in a 39 % and OTC-A10 in a 20 % larger area under the serum concentration-time curve, as compared to OTC-C (P < 0.05). The recorded tissue reaction in the form of swelling during the first week following injection of OTC-A5 averaged 72 % of that after OTC-C (P < 0.01), while the mean swelling after OTC-A10 was 81 % of the corresponding value after OTC-C (P < 0.05). The OTC residue levels at the sites of injection were lower after OTC-A5, but none of the preparations resulted in OTC residues exceeding 0.3 mg at 28 days and about 0.15 mg at 42 days after injection. The pathological changes at the site of injection were somewhat more pronounced in those calves which received OTC-C. Accordingly, these results give some support to the claims that Aquacycline® offers advantages with respect to absorption characteristics and tissue tolerance.     

Plasma concentrations of oxytetracycline in swine after administration of the drug intramuscularly and orally in feed

Four pigs were used in a 2 X 2 crossover study to determine plasma oxytetracycline (OTC) concentration and OTC pharmacokinetic variables after IM administration of 2 OTC preparations--long acting OTC and a 100-mg of OTC/ml solution (OTC-LA and OTC-100, respectively)--at a dosage of 20 mg/kg of body weight. In a second study, 3 additional pigs were given ad libitum access to feed containing pure OTC (0.55 g/kg of feed). The mean (+/- SD) peak plasma OTC concentration after OTC-LA administration was 6.0 +/- 2.2 micrograms/ml at 30 minutes; the mean peak plasma OTC concentration after OTC-100 administration was 6.7 +/- 3.4 micrograms/ml at 90 minutes. Mean plasma OTC concentration after oral OTC administration in feed peaked at 0.4 micrograms/ml 48 hours after access to OTC-medicated feed and decreased to 0.25 micrograms/ml by the end of that study. Mean plasma OTC concentration was maintained at greater than 0.5 micrograms/ml for less than 48 hours after OTC-LA administration and for less than 36 hours after OTC-100 administration. Mean plasma OTC concentration decreased to less than 0.2 micrograms/ml by 72 hours after IM administration of either product. Calculation of area under the plasma OTC concentration-time curve (AUC) did not reveal significant difference between the 2 OTC formulations. There also was not significant difference (between OTC-LA and OTC-100) in the value of the disappearance rate constant after administration of either OTC formulation. The data did not indicate significant pharmacologic advantage of OTC-LA, compared with OTC-100, when either formulation was administered IM at a dosage of 20 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Some Pharmacokinetic Parameters and Dosage Regimens for a Long-Acting Formulation of Oxytetracycline in 6- to 8-Month-Old Male Calves

A two-way crossover study was conducted in crossbred male calves (6–8 months old) to determine the bioavailability, pharmacokinetics and dosage regimens for a long-acting formulation of oxytetracycline (OTC-LA). The half-lives of oxytetracycline after intravenous and intramuscular administration were 7.8 h and 24 h, respectively. The volume of distribution and total body clearance values of the drug were 0.86±0.07 L and 76.1±3.3 (ml/h)/kg, respectively. The maximum concentration of the drug in the serum (4.7–7.4 g/ml) was achieved 8–10 h after intramuscular administration. The minimum therapeutic serum concentration of drug of 0.5 g/ml was maintained between 15 min and 84 h after intramuscular administration. The intramuscular bioavailability of the drug was 89.1±4.2%. The dosage regimens to maintain the minimum therapeutic serum concentrations of OTC following intramuscular administration of OTC-LA were computed.     

Pharmacokinetics of oxytetracycline after intramuscular administration with lidocaine in sheep, comparison with a conventional formulation

The pharmacokinetic behaviour of oxytetracycline (OTC) was studied in 11 sheep after intravenous and intramuscular administration at a single dosage of 20 mg kg⁻¹ bodyweight. A conventional formulation was injected by the intravenous route and two different preparations were administered by the intramuscular route: a conventional formulation (T-100) and an aqueous solution of OTC with lidocaine (1 per cent) (OTC-Q. The objective was to determine whether there are differences between both formulations in the disposition kinetics of OTC after intramuscular administration to sheep. After intravenous administration of the conventional formulation, plasma oxytetracycline concentrations were best fitted to an open two-compartment model. Mean apparent volume of distribution was 0·77±0·02 litre kg⁻¹ and the harmonic mean half-life was three hours. The OTC transfer process between central and peripheral compartments was fast and that did not influence the elimination process. After intramuscular administrations of both formulations, half-lives were longer than after intravenous administration (mean values of 14·1 and 58·2 hours for T-100 and OTC-L respectively). In both cases, a biphasic absorption, a ‘flip-flop’ model and a complete bioavailability were found. OTC-L provided therapeutic plasma concentrations over 0·5 μg ml⁻¹ (the minimum inhibitory concentration for most susceptible pathogens) for a longer period of time than T-100 (72 hours compared with 36 or 48 hours).     

Cortisol Concentrations in Well‐Regulated Dogs with Hyperadrenocorticism Treated with Trilostane

Background

There are no clear treatment guidelines for dogs with clinically well‐regulated hyperadrenocorticism in which serum cortisol concentrations before and after an ACTH stimulation test performed 3–6 hours after trilostane administration are < 2.0 μg/dL.

Objective

To determine if serum cortisol concentrations measured before (Pre1) and after (Post1) ACTH stimulation at 3–6 hours after trilostane administration are significantly lower than cortisol concentrations measured before (Pre2) and after (Post2) ACTH stimulation 9–12 hours after trilostane administration, in a specific population of dogs with clinically well‐regulated hyperadrenocorticism and Pre1 and Post1 <2 μg/dL.

Animals

Thirteen client‐owned dogs with clinically well‐regulated hyperadrenocorticism and Pre1 and Post1 serum cortisol concentrations <2.0 μg/dL 3–6 hours after trilostane administration.

Methods

Prospective study. Dogs had a second ACTH stimulation test performed 9–12 hours after trilostane administration, on the same day of the first ACTH stimulation test. Cortisol concentrations before and after ACTH stimulation were compared using a paired t‐test.

Results

Cortisol concentrations before (1.4 ± 0.3 μg/dL) and after the first stimulation (1.5 ± 0.3 μg/dL, mean ± SD) were significantly lower than cortisol concentration before the second stimulation (3.3 ± 1.6 μg/dL, P = .0012 each). Cortisol concentration before the first stimulation was also significantly lower than cortisol concentration after the second stimulation (5.3 ± 2.4 μg/dL, P = .0001).

Conclusions and clinical importance

In dogs with clinically well‐regulated, trilostane‐treated, hyperadrenocorticism, and cortisol concentrations <2 μg/dL before and after the first stimulation, a second ACTH stimulation test performed 9–12 hours after treatment can result in higher cortisol concentrations that could support continued trilostane treatment.     

Comparative pharmacokinetics and bioavailability of eight parenteral oxytetracycline‐10% formulations in dairy cows

Summary

In plasma and milk the oxytetracycline (OTC) concentrations were determined following a single intramuscular administration of eight 10%‐formulations to dairy cows at a dose of approximately 5 mg/kg. Two of these formulations were injected intravenously to obtain reference values of the drug's pharmacokinetic parameters. The eight formulations were compared and evaluated pharmacokinetically with respect to absorption rate, peak plasma and milk OTC concentrations, biological half‐life, and relative bioavailability. The mean maximum plasma OTC concentrations, ranging from 2.0 to 4. 1 μg/ml, were achieved between 4 and 12 hours post injection, depending on the formulation involved. The mean maximum milk OTC concentrations, in the range between 0.92 and 1.43 μg/ml, were achieved 12 to 24 h p. i. The OTC milk concentration‐time profile ran parallel to the OTC plasma concentration‐time profile.

After intravenous administration the time for the appearance of OTC in milk was shorter (1–2 hours p.i.), the peak milk OTC concentration was higher (1.7–1.9 μg/ml) and achieved earlier (6–8 h p.i.). and the OTC persistence in milk shorter than after i.m. administration. Formulations exhibiting the lowest clinically noticeable irritation showed the most favourable pharmacokinetic characteristics: rapid absorption with the highest peak plasma OTC concentrations and good bioavailability.

The plasma and milk protein binding for OTC was respectively 71.7± 7.4% and 84.8 ± 5.45%. Withdrawal times for milk and edible tissues are presented on the basis of preset tolerance or detection limits.     

Penetration of oxytetracycline into the nasal secretions and relationship between nasal secretions and plasma oxytetracycline concentrations after oral and intramuscular administration in healthy pigs

Bimazubute, M., Cambier, C., Baert, K., Vanbelle, S., Chiap, P., Gustin, P. Penetration of oxytetracycline into the nasal secretions and relationship between nasal secretions and plasma oxytetracycline concentrations after oral and intramuscular administration in healthy pigs. J. vet. Pharmacol. Therap. 34 , 176–183. The penetration of oxytetracycline (OTC) in plasma and nasal secretions of healthy pigs was evaluated during the first study, in response to oral dose of 20 mg of OTC per kg of body weight (bwt) per day as a 400 mg/kg feed medication (n = 5) and to intramuscular (i.m.)‐administered formulations at 10 mg/kg bwt (n = 5), 20 mg/kg bwt (n = 5), 40 mg/kg bwt (n = 5). Concentrations of OTC in plasma and nasal secretions were determined by a validated ultra‐high performance liquid chromatography associated to tandem mass spectrometry method (UPLC/MS/MS). The objectives were to select the efficacy treatment and to evaluate the possibility to predict nasal secretions concentrations from those determined in plasma. The animals were housed together in each experiment. In each group, the treatment was administered once daily during 6 consecutive days, and nasal secretions and plasma were collected after 4 and 24 h at day 2 and day 6. For oral administration, only one medicated feed was prepared and distributed to all the animals together and was consumed in approximately 1 h. To meet recommendations of efficacy for OTC in nasal secretions, only the i.m. of 40 mg/kg bwt associated to an inter‐dosing interval of 24 h provides and maintains concentrations in nasal secretions ≥1 μg/mL, appropriate to the MIC 50 and 90 of Pasteurella multocida and Bordetella bronchiseptica, respectively, the main pathological strains in nasal secretions. It has been demonstrated that, using a generalized linear mixed model (GLMM), OTC in the nasal secretions (μg/mL) can be predicted taking into account the OTC concentrations in plasma (μg/mL), according to the following equation: OTC_{nasal secretions} = 0.28 OTC_plasma?1.49. In a second study, the pharmacokinetic behaviour of OTC in plasma and nasal secretions of healthy pigs was investigated, after single‐dose i.m. of 40 mg/kg bwt of the drug. Blood samples and nasal secretions were collected at predetermined times after drug administration. The data collected in 10 pigs for OTC were subjected to non‐compartmental analysis. In plasma, the maximum concentration of drug (C_max), the time at which this maximum concentration of drug (T_max) was reached, the elimination half‐life (t½) and the area under the concentration vs. time curve (AUC) were, respectively, 19.4 μg/mL, 4.0, 5.1 h and 150 μg·h/mL. In nasal secretions, C_max, T_max, t½ and AUC were, respectively, 6.29 μg/mL, 4.0, 6.6 h and 51.1 μg·h/mL.     

Muscle tissue kinetics of oxytetracycline following intramuscular and oral administration at two dosages to giant freshwater shrimp (Macrobrachium rosenbergii)

The giant river shrimp (Macrobrachium rosenbergii), a native species of Thailand, is either exported for commercial purposes or supplied to meet the local requirements in Thailand. Limited pharmacokinetic information of the major antibiotic, oxytetracycline (OTC), is available for this freshwater shrimp. The purpose of the present study was to investigate the muscle tissue kinetics of OTC in M. rosenbergii following either intramuscular (i.m.) or oral (p.o.) administration at two dosages of 11 and 22 mg/kg body weight (b.w.). The concentration of OTC in shrimp tissues was measured using high‐performance liquid chromatography (HPLC) equipped with a fluorescence detector. Muscle tissue concentrations were below the detection limit (LOD, 0.1 μg/g) after 96 and 120 h, following i.m. and p.o. administration, respectively. Peak muscle concentrations (C_max) were 3.47 and 1.73 μg/g after i.m. and p.o. administration at a single dose of 11 mg/kg b.w. whereas they were 6.03 and 2.51 μg/g at a single dose of 22 mg/kg b.w., respectively. A noncompartment model was developed to describe the pharmacokinetics of OTC in the giant freshwater shrimp. The terminal half‐lives of OTC were 28.68 and 28.09 h after i.m. and p.o. administration at a single dose of 11 mg/kg b.w., but 29.95 and 27.03 h at a single dose of 22 mg/kg b.w., respectively. The relative bioavailability was 82.32 and 64.67% following i.m. and p.o. administration, respectively. Based on the pharmacokinetic data, i.m. and p.o. administration with OTC at a dose of 11 mg/kg b.w. would be appropriate for use in giant freshwater shrimp farming. To avoid the OTC residue in shrimp muscle, it should take at least seven half‐lives (8 days) to wash out the drug from the muscle of M. rosenbergii.     

Pharmacokinetics of Single‐Dose Rectal Zonisamide Administration in Normal Dogs

Background

Few medications are available for parental administration to animals with seizures. Rectal administration of medications is often used if the animal cannot be administered oral medications.

Hypothesis/Objectives

To determine the pharmacokinetic differences in zonisamide when administered rectally in either of 2 vehicles and PO to dogs.

Animals

Eight healthy research dogs.

Methods

Randomized cross‐over design. Zonisamide, 10 mg/kg, was administered rectally in polyethylene glycol (PEG‐R), rectally in water (H₂O‐R), and as an oral capsule. Plasma zonisamide concentrations were measured until 72 hours after administration. Zonisamide was quantitated by HPLC and plasma concentration versus time curve data was analyzed by using noncompartmental modeling.

Results

Mean maximum plasma zonisamide concentrations (μg/mL) were significantly higher after oral administration (11.56 ± 4.04) compared to H₂O‐R (5.00 ± 1.83) (P = .004). Disappearance half‐life (hours) and mean time to maximum concentration (hours) were not significantly different between methods of administration. Mean relative bioavailability of PEG‐R (85 ± 69%) was significantly higher than that of H₂O‐R (53 ± 37%) (P = .039). Dogs tolerated all dosing forms with no evidence of adverse effects.

Conclusions and Clinical Importance

The vehicle in which zonisamide is dissolved influences rectal bioavailability, with PEG preferred to H₂O‐R. Because of the prolonged time to maximum concentration, rectal administration of zonisamide should not be used to treat status epilepticus in dogs. A dose higher than what was used in this study might be necessary, if currently recommended minimum therapeutic concentrations (10 μg/mL) are to be achieved with a single‐dose administration.     

Pharmacokinetics and renal clearance of oxytetracycline in piglets following intravenous and oral administration

Summary

The pharmacokinetics of oxytetracycline (OTC) in three weaned piglets was studied following three routes of administration: intravenously, orally as drench, both at a dose of 20 mg/kg, and orally as medicated (400 ppm OTC) pelleted feed administered during 3 consecutive days. Analysis of the intravenous data according to the three compartment pharmacokinetic model revealed that OTC was well distributed in the body (Vie 1.621/kg), had an overall body clearance of 0.25 litre/kg/h, and the elimination half‐lives were in the range between 11.6 and 17.2 hrs.

The mean OTC binding to plasma proteins was 75.5 ± 4%. Following the drench route of administration the maximum plasma OTC concentration was achieved between 1 and 5 h post application and ranged between 1.18 and 1.41 μg/ml. The mean maximum plasma OTC concentration during medicated feed administration was 0.20 ± 0.06 μg/ml, which was achieved approximately 30 hours after the onset of the administration. A steady state OTC plasma level (approximately 0.2 μg/ml) was maintained till the end of the trial. Within 48 hours after cessation of medicated feed administration the plasma OTC levels were beneath 0.06 μg/ml. The mean OTC bioavailabilities of the oral routes were low: after the drench route of administration 9.0 ± 0.67%, and after medicated pelleted feed administration 3.69 ± 0.8%.

The mean OTC renal clearances of each piglet ranged between 10.1 and 13.9 ml/min/kg (based on free OTC plasma fractions). The renal OTC clearance values were urine flow dependent in all piglets and significantly correlated with the renal creatinine clearance (P< 0.005), being 3–5 times higher than the latter. It is concluded that in piglets OTC is excreted mainly by glomerular filtration and partly by tubular secretion. The potential clinical efficacy of 400 ppm OTC as medicated feed with respect to treatment, e.g. atrophic rhinitis, is discussed.     

Correlation between oral fluid and plasma oxytetracycline concentrations after intramuscular administration in pigs

The penetration of oxytetracycline (OTC) into the oral fluid and plasma of pigs and correlation between oral fluid and plasma were evaluated after a single intramuscular (i.m.) dose of 20 mg/kg body weight of long‐acting formulation. The OTC was detectable both in oral fluid and plasma from 1 hr up to 21 day after drug administration. The maximum concentrations (C_max) of drug with values of 4021 ± 836 ng/ml in oral fluid and 4447 ± 735 ng/ml in plasma were reached (T_max) at 2 and 1 hr after drug administration respectively. The area under concentration–time curve (AUC), mean residence time (MRT) and the elimination half‐life (t_1/2β) were, respectively, 75613 ng × hr/ml, 62.8 hr and 117 hr in oral fluid and 115314 ng × hr/ml, 31.4 hr and 59.2 hr in plasma. The OTC concentrations were remained higher in plasma for 48 hr. After this time, OTC reached greater level in oral fluid. The strong correlation (r = .92) between oral fluid and plasma OTC concentrations was observed. Concentrations of OTC were within the therapeutic levels for most sensitive micro‐organism in pigs (above MIC values) for 48 hr after drug administration, both in the plasma and in oral fluid.     

Disposition of a long‐acting oxytetracycline formulation in Thai swamp buffaloes (Bubalus bubalis)

The present study aimed to characterize the pharmacokinetic profile of oxytetracycline long‐acting formulation (OTC‐LA) in Thai swamp buffaloes, Bubalus bubalis, following single intramuscular administration at two dosages of 20 and 30 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 504 h. The plasma concentrations of OTC were measured by high‐performance liquid chromatography (HPLC). The concentrations of OTC in the plasma were determined up to 264 h and 432 h after i.m. administration at doses of 20 and 30 mg/kg b.w., respectively. The C_max values of OTC were 12.11 ± 1.87 μg/mL and 12.27 ± 1.92 μg/mL at doses of 20 and 30 mg/kg, respectively. The AUC_last values increased in a dose‐dependent fashion. The half‐life values were 52.00 ± 14.26 h and 66.80 ± 10.91 h at doses of 20 and 30 mg/kg b.w, respectively. Based on the pharmacokinetic data and PK–PD index (T > MIC), i.m. administration of OTC at a dose of 30 mg/kg b.w once per week might be appropriate for the treatment of susceptible bacterial infection in Thai swamp buffaloes.     

Residues from long-acting antimicrobial preparations in injection sites in cattle

Objective To investigate tissue residues of two longacting oxytetracycline (OTC) preparations in cattle.
Design A randomised drug residue trial.  

Animals

Two hundred and forty beef cattle in 24 groups of ten.
Procedure Two blind-coded 200 mg/mL OTC preparations were used in five treatment regimens of various combinations of injection sites (from one to five) and administrations (one or two). Five cattle from each group were slaughtered at 21, 30 and 60 days after injection and the injection site, urine, kidney and diaphragm muscle analysed for residues.
Results The OTC concentration exceeded the maximum residue limit in kidney in animals slaughtered 21 days after treatment, which is the prescribed withholding period. Concentration at the injection site was much greater than the maximum residue limit 30 days post-treatment, but not 45 days post-treatment. The residue was smaller when OTC had been injected in multiple sites. There was no difference between the two OTC preparations.
Conclusion A review of the maximum injection volume, site of injection and the withholding period is needed for long-acting OTC formulations.     

Serum pharmacokinetics of oxytetracycline in sheep and calves and tissue residues in sheep following a single intramuscular injection of a long-acting preparation

The pharmacokinetics of a long‐acting oxytetracycline (OTC) formulation (Liquamycin® LA‐200®) injected intramuscularly (i.m.) at a dose of 20 mg/kg were determined in four calves and 24 sheep to determine if the approved label dose for cattle provided a similar serum time/concentration profile in sheep. The AUC for the calves was 168±14.6 (μg ? h/mL) and was significantly less than the AUC for sheep (209±43 μg ? h/mL). Using the standard two‐stage approach and a one‐compartment model, the mean Cmax for the calves was 5.2±0.8 μg/mL, and for the sheep was 6.1±1.3 μg/mL. The mean terminal phase rate constants were 0.031 and 0.033 h, and the Vdss were 3.3 and 3.08 L/kg for the calves and sheep respectively. Analysis of the data using the standard two‐stage approach, the naive pooled‐data approach and a population model gave very similar results for both the cattle and sheep data. Sheep tissue residues of OTC in serum, liver, kidney, fat, muscle and injection site were measured at 1, 2, 3, 5, 7 and 14 days after a single i.m. injection of 20 mg/kg OTC. Half‐lives of OTC residues in the tissues were 38.6, 33.4, 28.6, 25.4, 21.3, and 19.9 h for injection site, kidney, muscle, liver, mesenteric fat and renal fat, respectively. The ratio of tissue to serum concentration was fairly consistent at all slaughter times, except for the fat and injection sites. The mean ratios were 1.72, 4.19, 0.11, 0.061, 0.84 and 827 for the liver, kidney, renal fat, mesenteric fat, muscle and injection sites, respectively. The tissue concentrations of OTC residues were below the established cattle tolerances for OTC in liver (6 p.p.m.), muscle (2 p.p.m.) and kidney (12 p.p.m.) by 48 h, and in injection site muscle by 14 days after the single i.m. injection of 20 mg/kg.     

Pharmacokinetics and bioavailability of doxycycline in ostriches (Struthio camelus) at two different dose rates

A bioavailability and pharmacokinetics study of doxycycline was carried out on 30 healthy ostriches after a single intravenous (IV), intramuscular (IM) and oral dose of 15 mg/kg body weight. The plasma doxycycline concentration was determined by HPLC/UV at 0 (pretreatment), 0.08, 0.25, 0.5 1, 2, 4, 6, 8, 12, 24 and 48 h after administration. The plasma concentration-time curves were examined using non-compartmental methods based on the statistical moment theory for only the higher dose. After IV administration, the elimination half-life (t_1/2β), mean residence time (MRT), volume of distribution at the steady-state (V_ss), volume of distribution (Vd_area) and total body clearance (Cl_B) were 7.67 ± 0.62 h, 6.68 ± 0.86 h, 0.86 ± 0.16 l/kg, 1.67 ± 0.52 l/kg and 2.51 ± 0.63 ml/min/kg, respectively. After IM and oral dosing, the mean peak plasma concentrations (C_max) were 1.34 ± 0.33 and 0.30 ± 0.04 µg/ml, respectively, which were achieved at a post-administration time (t_max) of 0.75 ± 0.18, 3.03 ± 0.48 h, respectively. The t_1/2β, Vd_area and Cl_B after IM administration were 25.02 ± 3.98 h, 23.99 ± 3.4 l/kg and 12.14 ± 1.71 ml/min/kg, respectively and 19.25 ± 2.53 h, 61.49 ± 7 l/kg and 40.19 ± 3.79 ml/min/kg after oral administration, respectively. The absolute bioavailability (F) of doxycycline was 5.03 and 17.52% after oral and IM administration, respectively. These results show that the dose data from other animals particularly mammals cannot be extrapolated to ostriches. Therefore, based on these results along with those reported in the literature, further studies on the pharmacokinetic/pharmacodynamic, in vitro minimum inhibitory concentration values and clinical applications of doxycycline in ostriches are required.     

Effect of Chronic Administration of Phenobarbital,or Bromide,on Pharmacokinetics of Levetiracetam in Dogs with Epilepsy

Background

Levetiracetam (LEV) is a common add‐on antiepileptic drug (AED) in dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs.

Hypothesis/Objectives

To evaluate the pharmacokinetics of LEV in dogs with epilepsy when administered concurrently with conventional AEDs.

Animals

Eighteen client‐owned dogs on maintenance treatment with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB–BR group, n = 6).

Methods

Prospective pharmacokinetic study. Blood samples were collected at 0, 1, 2, 4, and 6 hours after LEV administration. Plasma LEV concentrations were determined by high‐pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations, using a noncompartmental method, and area‐under‐the‐curve (AUC) calculated to the last measured time point.

Results

Compared to the PB and PB–BR groups, the BR group had significantly higher peak concentration (C _max) (73.4 ± 24.0 versus 37.5 ± 13.7 and 26.5 ± 8.96 μg/mL, respectively, P < .001) and AUC (329 ± 114 versus 140 ± 64.7 and 98.7 ± 42.2 h*μg/mL, respectively, P < .001), and significantly lower clearance (CL/F) (71.8 ± 22.1 versus 187 ± 81.9 and 269 ± 127 mL/h/kg, respectively, P = .028).

Conclusions and Clinical Importance

Concurrent administration of PB alone or in combination with bromide increases LEV clearance in epileptic dogs compared to concurrent administration of bromide alone. Dosage increases might be indicated when utilizing LEV as add‐on treatment with phenobarbital in dogs.     

Excitability scores of goats administered ascorbic acid and transported during hot-dry conditions

In this study, we investigated the effect of ascorbic acid (AA) administration on goat excitability due to transportation. Ten goats administered AA (p.o.) at 100 mg/kg of body weight before transportation served as the experimental group, and seven goats administered only 10ml/kg of sterile water (p.o.) served as controls. Excitability scores were recorded for each goat; when weighed, before, immediately after, and 3 h after 8 h of transportation. A score of one to four was allocated to each goat; higher scores represent greater excitability. Immediately after transportation, excitability scores decreased significantly, especially those of control goats (p < 0.001). At 3 h post-transportation, the excitability scores of animals in the experimental group were not significantly (p>0.05) different from their pre-transportation normal values, whereas those of control goats were significantly lower (p < 0.01). The correlation i.e. the relationship between excitability score values and percent excitability (percentage of goat with particular excitability score) for different excitability score group 3 h post-transportation was positive and highly significant (p < 0.001), in both experimental and control goats. Our results indicate that road transportation induces considerable stress (depression) in goats as evidenced by a lower excitability score post-transportation. Moreover, the administration of AA pre-transportation facilitated the transition from a state of depression to excitation. In conclusion, AA administration to animals prior to transportation may ameliorate the depression often encountered after road transportation.     

Effect of Feeding an Iodine‐Restricted Diet in Cats with Spontaneous Hyperthyroidism

Background

Exclusive feeding of an iodine‐restricted diet has been proposed as a method for controlling clinical manifestations of hyperthyroidism in hyperthyroid cats.

Objectives

To determine the effect of feeding an iodine‐restricted diet on TT4 concentrations and clinical signs in cats with spontaneous hyperthyroidism.

Animals

Forty‐nine client‐owned cats with spontaneous hyperthyroidism.

Methods

Retrospective case series. Hyperthyroid cats were exclusively fed a commercially available iodine‐restricted diet. Clinical response was assessed by change in weight and heart rate and serum TT4, blood urea nitrogen (BUN), and creatinine concentrations at various times during dietary management (21–60 days, 60–180 days).

Results

Serum TT4 normalized in 20/48 cats (42%) and 39/47 cats (83%) at 21–60 days and 61–180 days, respectively. Cats in which the TT4 concentrations were still above reference range at 21–60 days had a significantly higher starting TT4 than those that normalized their TT4 levels during the same time period (P = .038). Body weight did not significantly increase (P = .34) nor heart rate decrease (P = .64) during the study. There was a significant decrease in serum creatinine (P = .028). Cats in the low reference range for serum TT4 concentrations did not have a significant increase in body weight (P = .41) nor creatinine (P = .54) when compared to those with high reference range.

Conclusions and Clinical Importance

Restricted‐iodine diets were effective at maintaining serum TT4 concentrations within reference ranges for a majority of cats with spontaneous hyperthyroidism over 1 year, although not all clinical signs of hyperthyroidism improved.     

Pharmacokinetics and residues in milk of oxytetracyclines administered parenterally to dairy goats

OBJECTIVE: To determine for two commercial preparations of oxytetracycline (OTC) the pharmacokinetic behaviour, the presence of detectable milk residues and the penetration in milk of OTC administered by intravenous (IV) (conventional formulation [CF]) and intramuscular (IM) routes (CF and long-acting [LA] formulations) in goats producing milk. The effects of these formulations on plasma activity values of creatine kinase (CK) and lactate dehydrogenase (LDH) were also determined as indicators of tissue damage. PROCEDURE: Five healthy lactating goats producing 1.5+/-0.5 L/d milk and weighing 56.0+/-4.8 kg were used. Single doses of OTC chlorhydrate (CF) were administered (20 mg OTC/kg) by IV (Trial 1 IV) and IM (Trial 1 IM) routes and OTC dehydrate (LA) by the IM route. The same goats were first given IV CF, then IM CF followed by IM LA with 3 weeks between each treatment. Blood and milk samples were taken. The quantification of OTC was performed by HPLC and the plasma activities of CK and LDH enzymes were determined by spectrophotometry. The presence of OTC residues in milk was determined by a commercial reagent. The plasma pharmacokinetic parameters were calculated using a two-compartment model. RESULTS: Estimates of kinetic variables following IV administration were: Vss= 400.0+/-120.0 mL/kg and CL= 110.0+/-14.0 (mL/h)/kg. The t(fi) for IV= 3.0+/-0.3 h; IM, CF = 10.5+/-2.1 h and IM, LA = 15.1+/-3.1 h. The concentration of OTC in milk at 48 h was: IV= 0.6+/-0.4; IM CF= 1.1+/-0.2 and at 72 h (IM LA)= 0.6+/-0.1 microg/mL and the penetration in milk of OTC was: IV= 70.0+/-18.0; IM CF= 79.0+/-14.0 and IM LA= 66.0+/-6.0%. The areas under the curve of CK and LDH activities in plasma were calculated by the trapezoidal method. Values of CK and LDH IM, LA were greater (P < 0.05) than those observed for IM, CF at 2 and 3 days after administration of the antibiotic. Finally, the bioavailability of OTC CF = 92.0+/-22.0 and LA= 78.0+/-23.0% was suitable for its usage by the IM route in lactating goats. CONCLUSION: Plasma concentration-time values of OTC administered parenterally in production dairy goats showed similar bioavailability for the two pharmaceutical preaprations. The presence of detectable residues in milk indicates that milk should not be used for human consumption for 2 and 3 days after administration of conventional and long-acting formulations, respectively. The increments in CK and LDH activities after the IM administration of LA are consistent with the presence of tissue damage provoked by the pharmaceutical preparations at the injection site.