Bioavailability of levamisole administered by subcutaneous and oral routes in rabbits

The bioavailability of levamisole in rabbits was determined after subcutaneous and oral administration at three dose levels of 12.5, 16.0 and 20.0 mg/kg. After non-compartmental analysis the mean values obtained were: C _max=3.54, 4.51 and 5.39 μg/ml; t _max= 12.0, 22.0 and 20.0 min; F = 134.8, 105.4 and 124.1% after subcutaneous administration for each dose, respectively, and C _max= 0.71, 1.32 and 1.77 μg/ml; t _max= 46.0, 96.0 and 84.0 min; F = 53.0, 62.0 and 80.7% after oral administration. The extent and rate of absorption from the two routes differed significantly, except for t _max at the 12.5 mg/kg dose. After compartmental analysis the pharmacokinetics of levamisole was characteristic of a two-compartment open model in 13 rabbits and of a one-compartment open model in two rabbits after subcutaneous administration, while it was two compartmental in nine and one compartmental in six rabbits after oral administration. The k_a values were 0.321, 0.145 and 0.145 min^-1 after subcutaneous administration and 0.054, 0.023 and 0.027 min¹ after oral administration. There were no significant differences between the values of C _max, t _max and AUC calculated by compartmental and non-compartmental analysis.     

Comparative pharmacokinetics of amikacin in Greyhound and Beagle dogs

The purpose of the study was to compare the pharmacokinetics of amikacin administered i.v., to Greyhound and Beagle dogs and determine amikacin pharmacokinetics administered subcutaneously to Greyhounds. Amikacin was administered i.v. at 10 mg/kg to six healthy Greyhounds and six healthy Beagles. The Greyhounds also received amikacin, 10 mg/kg s.c. Plasma was sampled at predetermined time points and amikacin concentrations determined by a fluorescence polarization immunoassay (FPIA).
The volume of distribution was significantly smaller in Greyhounds (mean = 176.5 mL/kg) compared to Beagles (234.0 mL/kg). The C ₀ and AUC were significantly larger in Greyhounds (86.03 μg/mL and 79.97 h·μg/mL) compared to Beagles (69.97 μg/mL and 50.04 h·μg/mL). The plasma clearance was significantly lower in Greyhounds (2.08 mL/min/kg) compared to Beagles (3.33 mL/min/kg). The fraction of the dose absorbed after s.c. administration to Greyhounds was 0.91, the mean absorption time was 0.87 h, and the mean maximum plasma concentration was 27.40 μg/mL at 0.64 h.
Significant differences in the pharmacokinetics of amikacin in Greyhounds indicate it should be administered at a lower dose compared to Beagles. The dose in Greyhounds to achieve a C _max: AUC  ≥ 8 for bacteria (with an MIC  ≤ 4 μg/mL) is 12 mg/kg q24 h compared to 22 mg/kg q24 in Beagles.     

Pharmacokinetics of total thyroxine in dogs after administration of an oral solution of levothyroxine sodium

Oral l -thyroxine ( l -T4) supplementation is used to replace thyroid hormone concentrations in dogs with hypothyroidism. The pharmacokinetics of l -T4 following administration of a solution (Leventa^®) was investigated in healthy dogs. l -T4 was absorbed fairly rapidly ( t _max 3 h). A mean bioavailability of 22% was calculated following a single oral administration of 40 μg l -T4/kg body weight. Repeated oral administration at the same dose for 14 consecutive days did not lead to any accumulation of T4 in serum. After intravenous administration of l -T4, a serum half-life of 11.6 h was calculated. Food intake concomitant with l -T4 oral administration delayed l -T4 absorption and decreased its rate and extent by about 45%. The relative bioavailability of l -T4 following administration of a tablet formulation was about 50% of that of the l -T4 solution. The pharmacokinetic properties of liquid l -T4 after oral administration support the use of a dose rate of 20 μg/kg once daily, as a starting dose for replacement therapy in dogs with hypothyroidism.     

The dose-related effects of phenylbutazone and a methylprednisolone acetate formulation (Depo-Medrol®) on cultured explants of equine carpal articular cartilage

The dose-related effects of phenylbutazone and Depo-Medrol® on chondrocyte viability and chondrocyte-mediated synthesis and depletion of proteoglycans were investigated using cultured explants of equine middle carpal joint articular cartilage. Explants from 12 horses (941 × 3 mm diameter) were cultured for a total of 5 days, which included 3 days' exposure to either phenylbutazone (0, 2, 20, 200 or 2000 μg/mL) or Depo-Medrol (0, 20, 200 or 2000 μg/mL). For each explant, amino sugar content was used as a measure of proteoglycan content, ³⁵S incorporation as a measure of the rate of proteoglycan synthesis and the number of pyknotic nuclei as a measure of cell death. During culture, control explants remained metabolically active and viable but suffered a net loss of proteoglycans. Proteoglycan loss was reduced by the presence of either phenylbutazone or Depo-Medrol. This effect was significant at clinically relevant concentrations of phenylbutazone (2–20 μg/mL), but not Depo-Medrol (20–200 μg/mL). Depo-Medrol caused a dose-dependent suppression of proteoglycan synthesis at all concentrations, but chondrocyte viability was affected only at the 2000 μg/mL dose. Phenylbutazone affected proteoglycan synthesis and cell viability only at the 2000 μg/mL concentration. At all concentrations, the anticatabolic effects of each drug influenced the proteoglycan content of the explants far more than did any antianabolic or cytotoxic drug effect. The results suggest that the therapeutic potential of both phenylbutazone and Depo-Medrol may not be restricted to their anti-inflammatory effects on the soft tissues of the joint.     

Prothrombotic and Inflammatory Effects of Intravenous Administration of Human Immunoglobulin G in Dogs

Background: Intravenous administration of human immunoglobulin G (hIVIgG) has been suggested to potentiate thromboembolism in dogs, but supportive scientific reports are lacking.
Objectives: To determine if hIVIgG therapy promotes hypercoagulability and inflammation in dogs.
Animals: Twelve healthy Beagle dogs.
Methods: Prospective, experimental trial. An hIVIgG/saline solution was infused IV at 1 g/kg BW over 8 hours to 6 dogs, and physiological saline was infused to the other 6 dogs. Blood samples were drawn before, during, and after infusion for serial measurement of indicators of coagulation and inflammation. Data were analyzed by 2-way repeated measures analysis of variance.
Results: Dogs administered hIVIgG developed mildly decreased blood platelet concentrations without thrombocytopenia (median, 200 × 10³/μL; range, 150–302 × 10³/μL; P < .01), leukopenia (median, 3.5 × 10³/μL; range, 20–62 × 10³/μL; P < .001), and mildly increased plasma total protein concentrations (median, 6.3 g/dL; range, 5.6–6.7 g/dL; P < .001). Administration of hIVIgG was also associated with increases in fibrin/fibrinogen degradation products in all dogs (either 5 μg/mL or 10 μg/dL), thrombin-antithrombin III complexes (median, 7.2 ng/mL; range, 4.9–14.2 ng/mL; P < .001), and C-reactive protein concentrations (median, 2.5 mg/dL; range, 0.5–4.3 mg/dL; P < .01).
Conclusion and Clinical Importance: Administration of hIVIgG to dogs promotes hypercoagulability and an inflammatory state. This should be further evaluated and considered when using hIVIgG in dogs with IMHA or other prothrombotic conditions.     

Metabolites of Monascus ruber in silages

A total of 233 silages were examined and found that Monascus ruber was present in 43 samples with counts between 1 × 10³ and 9 × 10⁶ colony-forming units (CFU)/g (mean: 2 × 10⁵ CFU/g). Monacolin K_L and the hydroxy acid monacolin K_A were detected by liquid chromatography-mass spectrometry in 45 and 50 of 233 samples at levels ranging from 25–15 600 and 28–65 400  μ g/kg, respectively. Citrinin was found with high-performance liquid chromatography-fluorescence detection (FLD) in 14 (6%) samples, the concentrations varied between 2.4 and 64.2  μ g/kg. The concentrations of citrinin were low and toxic effects are not anticipated. Monacolin K_A and monacolin K_L occur frequently and in considerable amounts in silages. These metabolites are believed to influence the metabolic activity of rumen anaerobic fungi resulting in a poorer digestion of crude fibre.     

Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs

Laber, G. Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs. J. vet. Pharmacol. Therap. 11 , 45–49.
Kinetic variables for tiamulin in the normal dog have been determined. Serum concentrations of tiamulin were compared after intramuscular (i.m.) and subcutaneous (s.c.) administration of a single dose of tiamulin. Following a single i.m. dose of 10 mg/kg body weight, the compound was calculated to have a C_max= 0.61 ± 0.15 μg/ml, a T _max= 6 h and a t _½= 4.7 ± 1.4 h. Tiamulin showed dose-dependent pharmacokinetics when given as a single s.c. dose of either 10 mg or 25 mg/kg body weight. For the lower dose, the values C_max= 1.55 ± 0.11 μg/ml, T _max= 8 h and 1 _max= 4.28 ± 0.18 h were obtained. For the higher dose C _max= 3.14 ± 0.04 μg/ml, T _max= 8 h and t _½= 12.4 ± 3.4 h were calculated. When tiamulin was administered subcutaneously at a dose rate of 10 mg/kg body weight, higher and better maintained serum levels were achieved than those following i.m. administration. After repeated s.c. doses no significant accumulation of tiamulin occurred. Assuming that a continuous effective serum concentration is necessary throughout the course of therapy, these data would indicate that tiamulin should be given every 24 h.     

Clinical Evaluation of a Novel Liquid Formulation of L-Thyroxine for Once Daily Treatment of Dogs with Hypothyroidism

Background: A liquid solution of levothyroxine (L-T4) is available for treatment of canine hypothyroidism.
Hypothesis: Once daily oral administration of a liquid L-T4 solution is effective and safe for controlling hypothyroidism in dogs.
Animals: Thirty-five dogs with naturally occurring hypothyroidism.
Methods: Dogs received L-T4 solution PO once daily at a starting dosage of 20 μg/kg body weight (BW). The dose was adjusted every 4 weeks, based on clinical signs and peak serum total T4 (tT4) concentrations. Target peak serum tT4 and thyroid stimulating hormone (TSH) concentrations, 4–6 hours posttreatment, were 35–95 nmol/L and < 0.68 ng/mL, respectively. Dogs were followed for up to 22 weeks after establishment of the maintenance dose.
Results: Clinical signs of hypothyroidism improved or resolved in 91% of dogs after 4 weeks of L-T4 treatment at 20 μg/kg once daily. The maintenance dose was established in 76, 94, and 100% of dogs after 4, 8, and 12 weeks of treatment, respectively. This was 20 μg L-T4/kg BW for 79% of the dogs, 30 μg/kg BW for 15%, and 10–15 μg/kg BW in the remaining 6%, once daily. Thereafter, median peak tT4 and TSH concentrations were 51 nmol/L and 0.18 ng/mL, respectively, and remained stable during the 22-week follow-up; clinical signs did not recur.
Conclusions and Clinical Importance: All of the hypothyroid dogs had rapid clinical and hormonal responses to supplementation with the PO-administered L-T4 solution. The starting dosage of 20 μg L-T4/kg BW once daily was suitable for 79% of dogs.     

Thermal antinociception after dexmedetomidine administration in cats: a dose-finding study

The optimum dose of dexmedetomidine for antinociception to a thermal stimulus was determined in a crossover study of 12 cats. In five treatment groups ( n  = 10 per group), dexmedetomidine was administered intramuscularly (i.m.) at 2, 5, 10, 20 and 40 μg/kg; positive and negative controls were administered buprenorphine (20 μg/kg, i.m.) and 0.9% saline (0.006 mL/kg, i.m.) respectively. Baseline thermal thresholds and visual analogue scale (VAS) sedation scores were obtained prior to drug treatment and then at regular intervals until 24 h after administration. The summary measures of overall mean thresholds and overall mean VAS scores were investigated using a univariate general linear model for multiple factors with post hoc Tukey's tests ( P  < 0.05). Only dexmedetomidine at 40 μg/kg displayed an analgesic effect (less than that of buprenorphine). The VAS for sedation did not significantly affect the thresholds obtained and treatment was the only significant factor to influence VAS. Dexmedetomidine resulted in higher VAS for sedation than saline and buprenorphine. Dexmedetomidine at 40 μg/kg significantly increased nociceptive thresholds compared with saline control, but less than buprenorphine. Dexmedetomidine produced dose-dependent sedation, but only the highest dose produced analgesia, suggesting that induction of analgesia requires the highest dose (or an additional analgesic) in the clinical setting.     

Plasma and urine disposition and dose proportionality of ceftiofur and metabolites in dogs after subcutaneous administration of ceftiofur sodium

Nine male dogs (10.3–13.5 kg body weight) were randomly assigned to three groups of three dogs each and administered ceftiofur sodium subcutaneously as a single dose of 0.22, 2.2, or 4.4 mg ceftiofur free acid equivalents/kg body weight. Plasma and urine samples were collected serially for 72 h and assayed for ceftiofur and metabolites (derivatized to desfuroylceftiofur acetamide) using high-performance liquid chromatography. Urine concentrations remained above the MIC ₉₀ for Escherichia coll (4.0 μg/mL) and Proteus mirabilis (1.0 μg/mL) for over 24 h after doses of 2.2 mg/kg (8.1 μg/mL) and 4.4 mg/kg (29.6 μg/mL), the interval between treatments for ceftiofur sodium in dogs, whereas urine concentrations 24 h after dosing at 0.22 mg/kg (0.1 mg/Ib) were below the MIC ₉₀ for E.coli and P. mirabills (0.6 μg/mL). Plasma concentrations were dose-proportional, with peak concentrations of 1.66 ± 0.0990 μg/mL, 8.91 ± 6.42 μg/mL, and 26.7 ± 1.07 μg/mL after doses of 0.22, 2.2, and 4.4 mg/kg, respectively. The area under the plasma concentration versus time curve, when normalized to dose, was similar across all dosage groups.     

Pharmacokinetics of single intravenous and single and multiple dose oral administration of rifampin in mares

The disposition of rifampin in six healthy mares after single intravenous (i.v.) and oral (p.o.) doses and after seven oral doses of 10 mg/kg administered twice a day was investigated using a high performance liquid chromatographic (HPLC) method. Pharmacokinetic variables for rifampin determined using the HPLC method were comparable to variables reported from earlier studies utilizing a microbiological assay. Desascetylrifampin, a major metabolite of the parent compound, could not be detected in the serum but was detected at low concentrations in urine. Mean trough concentrations of rifampin increased from the first to the second dose of the multiple dose oral study and then remained unchanged through 72 h. At 84 h after the first dose (i.e. 12 h after the final dose) the rifampin concentration was significantly decreased ( P = 0.001). The harmonic mean of the half-life of rifampin decreased significantly from 13.3 h after a single oral dose of 7.99 h after the seventh oral dose. The mean serum protein binding of rifampin over the concentration range of 2–20 μg/ml was 78%. Mean trough serum concentrations of unbound rifampin after multiple oral doses ranged from 0.67 μg/ml at 24 h to 0.40 μg/ml at 72 h. The mean unbound serum rifampin concentration at 84 h (i.e., 12 h after the final dose) was 0.30 μg/ml. Trough concentrations and the 84-h sample concentration of unbound rifampin exceeded the minimum inhibitory concentration for most gram positive bacterial isolates from horses reported in this study. All organisms with minimum inhibitory concentrations less than 0.125 μg/ml were considered susceptible.
Based on the pharmacokinetics of rifampin after p.o. administration, we concur with the current dosage recommendation of 10 mg/kg twice a day by mouth. At this dose, most streptococci, Rhodococcus equi , and coagulase-positive staphylococci would be considered susceptible to rifampin.     

Florfenicol pharmacokinetics in lactating cows after intravenous, intramuscular and intramammary administration

Pharmacokinetics of florfenicol 30% injectable solution was determined in lactating cows after intravenous, intramammary and intramuscular administration. Serum concentration-time data generated in the present study were analysed by non-compartmental methods based on statistical moment theory. Florfenicol half-life was 176 min, mean residence time 129 min, volume of distribution at steady-state 0.35 L/kg, and total body clearance 2.7 mL/min·kg after intravenous administration at 20 mg/kg. The absorption after intramuscular administration appeared slow and the kinetic parameters and the serum concentration vs. time curve were characteristic of absorption rate-dependent elimination. The absorption after intramammary administration of florfenicol at 20 mg/kg was good (53.9%) and resulted in serum concentrations with apparent clinical significance. The intramammary administration resulted in serum florfenicol concentrations that were significantly higher than the respective serum concentrations following Intravenous administration 4 h after administration and thereafter. Florfenicol absorption was faster from the mammary gland than from the muscle. The maximum serum concentrations ( C _max) were 6.9 μg/mL at 360 min after intramammary administration and 2.3 μg/mL at 180 min after intramuscular administration. The bioavailability of florfenicol was 54% and 38% after intramammary and intramuscular administration, respectively. The C _max in milk was 5.4 μg/mL at 180 min after intravenous and 1.6 μg/mL at 600 min after intramuscular administration.     

Retinol-Binding Protein in Serum and Urine of Hyperthyroid Cats before and after Treatment with Radioiodine

Background: Retinol-binding protein (RBP) is suggested as a clinically useful marker of renal function in cats.
Hypothesis: Serum and urinary RBP concentrations in hyperthyroid (HT) cats differ from those in healthy (H) cats; radioiodine (¹³¹I) treatment influences serum and urinary RBP concentrations in HT cats.
Animals: Ten HT and 8 H cats.
Methods: RBP concentration was evaluated in feline serum and urine samples from a prospective study.
Results: There was a significant ( P = .003) difference in the urinary RBP/creatinine (uRBP/c) ratios of H (−) and untreated HT (1.4 ± 1.5 × 10⁻² μg/mg) cats. Serum total thyroxine concentration (1.8 ± 1.9 μg/dL, 24 weeks) and uRBP/c (0.6 ± 1.0 × 10⁻² μg/mg, 24 weeks) decreased significantly ( P < .001) in HT cats at all time points after treatment with ¹³¹I, and these variables were significantly correlated with one another ( r = 0.42, P = .007). Serum RBP concentrations from HT cats (199 ± 86 μg/L) did not differ significantly ( P = .98) from those of H cats (174 ± 60) and did not change after treatment with ¹³¹I (182 ± 124 μg/L, P = .80).
Conclusion and Clinical Importance: The presence of urinary RBP in HT cats is a potential marker of tubular dysfunction that is correlated to thyroid status, although it is independent of circulating RBP concentrations. The decreased uRBP/c combined with the absence of changes in serum RBP after treatment suggests that the suspected tubular dysfunction was partly reversible with treatment of ¹³¹I.     

High performance liquid chromatography and pharmacokinetics of the non-steroidal anti-inflammatory drug oxindanac in calves

A high-performance liquid chromatographic method for the determination of the non-steroidal anti-inflammatory drug, oxindanac, in calf plasma is described. Recoveries over the concentration range 0.3 75 to 62.5 μg/ml were 90.2–107.8% with interassay coefficients of variation of 2.1–22.3%. The limit of detection was estimated as 0.10 μg/ml and the limit of quantification calculated to be 0.24 pg/ml in a 1 ml plasma sample. This method was used to establish the pharmacokinetics following intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administration to calves of oxindanac at a dose rate of 2 mg/kg. The elimination t ¹/₂, was long ( t 1/2 21.2 h after i.v. injection) and absorption was rapid (t¹/_2B 0.072 h) and complete ( F > 100%) following i.m. administration. Bioavailability was incomplete ( F = 66.6%) following p.o. administration to calves that had been fed on milk, and Wagner-Nelson analysis revealed twoabsorption phases ( t ¹/₂'s 0.20 and 1.9 h). Oxindanac produced long-lasting inhibition of serum TxB₂ production, with mean k_max values (% inhibition) of 96.8, 94.1 and 81.3 following i.v., i.m. and p.0. administration, respectively. A single i.v. or i.m. injection of 2 mg/kg oxindanac will probably be active in calves for at least 36–48 h.     

Pharmacokinetics, bioavailability and dosage regimen of sulphadiazine (SDZ) in camels (Camelus dromedarius)

The pharmacokinetics of sulphadiazine (SDZ) (100 mg/kg, body weight) were investigated in six camels ( Camelus dromedarius ) after intravenous (i.v.) and oral (p.o.) administration. Following i.v. administration, the overall elimination rate constant (β) was 0.029±0.001/h and the half-life ( t _½β) was 23.14±1.06 h. The apparent volume of distribution ( V d_(area)) was 0.790±0.075 L/kg and the total body clearance ( Cl _B) was 23.29±2.50 mL/h/kg. After p.o. administration, SDZ reached a peak plasma concentration ( C _max(cal.)) of 62.93±2.79 μg/mL at a post injection time of ( T _max(cal.)) 22.98±0.83 h. The elimination half-life was 19.79±1.22 h, not significantly different from that obtained by the i.v. route. The mean absorption rate constant (K_a) was 0.056±0.002 h⁻¹ and the mean absorption half-life ( t _½Ka) was 12.33±0.37 h. The mean availability ( F ) of sulphadiazine was 88.2±6.2%.
  To achieve and maintain therapeutically satisfactory plasma SDZ levels of 50 μg/mL, the priming and maintenance doses would be 80 mg/kg and 40 mg/kg intravenously and 90 mg/kg and 45 mg/kg orally, respectively, to be repeated at 24 h intervals.     

Gentamicin sulfate in the horse: serum, synovial, peritoneal, and urine concentrations after single dose intramuscular administration

Ten healthy adult mares were given a single intramuscular dose (2.2 mg/kg) of gentamicin sulfate. Over a 48-h period, gentamicin concentrations were measured serially in the serum of all ten mares and in synovial fluid, peritoneal fluid, and urine of six of the mares. The mean peak serum gentamicin concentration was 5.73 μg/ml at 1 h. Gentamicin was detected in synovial fluid and peritoneal fluid, with mean peak gentamicin concentrations of 2.41 μg/ml and 3.92 μg/ml, respectively, observed at 2 h. These concentrations declined in parallel with serum concentrations and were not measurable at 48 h. Urine gentamicin concentration was relatively high, with a mean peak concentration of 424.9 μg/ml at 1 h after drug administration.     

Plasma/muscle ratios of sulfadimethoxine residues in channel catfish (Ictalurus punctatus)

Channel catfish ( n = 84) maintained at a water temperature of 27°C were used in a feeding study to determine the plasma to muscle concentration ratios of sulfadimethoxine (SDM) and 4-N-acetylsulfadimethoxine residues. Sulfadimethoxine medicated feed was provided free choice at 42 mg SDM/kg body weight once daily for 5 days and the plasma and muscle concentrations of SDM were determined at selected withdrawal times (6, 12, 24, 48, 72, and 96 hours) following the last dose. Considerable variation in total SDM tissue concentration among fish within a sampling period was observed. For fish ( n = 12) at six hours post-dose, total SDM concentrations ranged from 1.4–24.8 μg/mL and 0.6–12.6 μg/g, with mean total SDM concentrations of 9.1 μg/mL and 5.3 μg/g for plasma and muscle, respectively. However, a mean plasma:muscle concentration ratio of 1.8:1 ± 0.3:1 was obtained over all concentrations and sampling periods. The plasma:muscle 95% t distribution interval for individual fish was 1.2:1 to 2.4:1. A correlation coefficient of 0.967 was obtained for the relationship between plasma and muscle total SDM concentration among individual fish ( n = 25). Results of this study indicate that plasma total SDM concentration may be used to identify samples containing violative SDM muscle residue. No fish contained total SDM muscle residues greater than the FDA tolerance (0.1 μg/g) by 48 hours following the final dose.     

Comparison of 2 Doses of Recombinant Human Thyrotropin for Thyroid Function Testing in Healthy and Suspected Hypothyroid Dogs

Background: Various protocols using different doses of recombinant human thyrotropin (rhTSH) in TSH stimulation testing have been described. However, the influence of TSH dosage on thyroxine (T4) concentration has not yet been evaluated in suspected hypothyroid dogs.
Objective: To evaluate the effectiveness of 2 doses of rhTSH.
Animals: Fifteen dogs with clinical signs consistent with hypothyroidism and abnormal stimulation results with 75 μg rhTSH and 18 clinically healthy dogs.
Methods: All dogs were stimulated with 75 and 150 μg rhTSH IV in a 1st and 2nd stimulation test, respectively. Blood samples were taken before and 6 hours after rhTSH administration for determination of total T4 concentration.
Results: Using the higher dose led to a normal test interpretation in 9 of the 15 dogs, in which stimulation had been abnormal using the lower dose. Based on follow-up information, hypothyroidism was excluded in 7 of these 9 dogs. In all 6 dogs with a blunted response to the higher dose, hypothyroidism could be confirmed. Healthy dogs showed significantly higher post-TSH T4 concentrations with the higher compared with the lower dose. Post-TSH T4 concentrations after TSH stimulation were not related to dogs' body weight in either healthy or diseased dogs.
Conclusions and Clinical Relevance: TSH dose significantly influenced test interpretation in suspected hypothyroid dogs. Differentiation between primary hypothyroidism and nonthyroidal disease was improved with 150 μg rhTSH. Because this effect was independent of the dogs' body weight, the higher dose is recommended in dogs that have concurrent disease or are receiving medication.     

Clinical pharmacology of polymyxin B, colistin and colistimethate in young dairy calves

The in vitro sensitivity of 592 Gram-negative bacteria isolated from cattle against polymyxin B was determined by the agar plate dilution method. The minimal inhibitory concentration of polymyxin B for all but ten of the isolates was ≤ 2.0 μg/ml and 75% of the isolates were inhibited at 1.0 μg of polymyxin B/ml or less. Intramuscular injections of polymyxin B, colistin and colistimethate (CMS) were given to veal calves once daily for 3 days. Mean peak serum drug concentrations were observed within 0.5–1 h after treatment and were between 2.7 and 4.7 μg/ml when polymyxin B and colistin were administered at a dose rate of 2.5 mg/kg/day, and between 5.3 and 7.5 μg/ml at dose rate of 5.0 mg/kg/day. When CMS was given at 5.0 mg/kg/day mean peak drug concentration was 14.1 μg/ml. The elimination half-life ( t _1/2) of polymyxin B and colistin was 4–5 h but was approximately 2 h for CMS. Kidney function tests, using the double isotope single-injection method, were performed before and after the course of antibiotic treatment. No changes were detected in the glomerular filtration rate (GFR) or the effective renal plasma flow (ERPF) and blood urea levels were not raised following treatment. Several calves treated with the higher doses of polymyxin B and colistin exhibited transient ataxia and apathy 2–4 h after treatment but clinical signs suggesting interference with neurological function were not observed after an equivalent dose of CMS was administered.     

Dose-sparing effects of romifidine premedication for thiopentone and halothane anaesthesia in the dog

Two intravenous doses of romifldine (40 and 80 μg/kg) and a placebo were compared as premedicants for anaesthesia induced with thiopentone and maintained using halothane in oxygen. Romifldine significantly and linearly reduced the induction dose of thiopentone; placebo-treated dogs required 15.1 ± 3.6 mg/kg, while dogs treated with 40 μg/kg and 80 μg/kg romifldine required 6.5 ± 1.6 and 3.9 ± 0.3 mg/kg thiopentone, respectively.
Romlfldine also significantly and linearly reduced the end tidal halothane concentration necessary to maintain a predetermined level of anaesthesia; piacebetreated dogs required 1.6 ± 0.3 per cent halothane, while dogs treated with 40 μg/kg and 80 μg/kg romifldine required 1.3 ± 0.4 and 0–8 ± 0.2 per cent, respectively.
Romifldine produced a significant shortening In the recovery from anaesthesia, and the higher dose of romlfldine significantly improved the overall quality of anaesthesia.