Pharmacokinetics of methimazole in normal cats and cats with hyperthyroidism

The intravenous and oral disposition of the antithyroid drug methimazole was determined in 10 clinically normal cats and nine cats with naturally occurring hyperthyroidism. After intravenous administration of 5 mg methimazole, the mean residence time was significantly (P less than 0.05) shorter in the cats with hyperthyroidism than in the normal cats, but there was no significant difference between the mean values for total body clearance (CL), steady state volume of distribution (Vdss), terminal elimination rate constant (ke), or serum terminal half-life (t1/2) in the two groups of cats. After oral administration, the mean bioavailability of methimazole was high in both the normal cats (77.6 per cent) and cats with hyperthyroidism (79.5 per cent). The values for mean residence time, ke and serum terminal t1/2 after oral dosing were significantly shorter in the cats with hyperthyroidism than in the normal cats. However, after oral administration of methimazole there were no significant differences between the mean values for CL, Vdss, bioavailability and maximum serum concentrations or the time for maximal concentrations to be reached in the two groups of cats. Overall, most pharmacokinetic parameters for methimazole were not altered by the hyperthyroid state. However, the cats with hyperthyroidism did show a trend toward faster elimination of the drug compared with the normal cats, similar to what has been previously described for the antithyroid drug propylthiouracil in cats. These results also indicate that methimazole is well absorbed when administered orally and has a higher bioavailability than that of propylthiouracil in cats with hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of controlled-release carbimazole tablets support once daily dosing in cats

Carbimazole, a prodrug of methimazole, is used in the treatment of hyperthyroidism in cats. The pharmacokinetics of methimazole was investigated in healthy cats following oral administration of 15 mg of carbimazole as a controlled-release tablet (Vidalta^®, Intervet). The controlled-release tablet did not produce a pronounced concentration peak and methimazole was present in the circulation for a sustained period, compared with a conventional tablet formulation. The time to reach peak concentrations after carbimazole administration was quite long (t_max 6 h). The absolute bioavailability of carbimazole was around 88 ± 11%. Repeated oral administration daily for 13 consecutive days did not lead to accumulation of methimazole in plasma. The extent of absorption of carbimazole was about 40% higher when administered to cats that had been fed compared to fasted cats. The relative oral bioavailability of methimazole following administration of the controlled-release tablets was similar to that of a conventional release formulation (83 ± 21%). The pharmacokinetics of this controlled-release formulation of carbimazole supports its use as a once daily treatment (both as a starting dose and for maintenance therapy) for cats with hyperthyroidism.     

Pharmacokinetics of fluconazole in cats after intravenous and oral administration

Fluconazole (100 mg) was administered to six adult cats as an intravenous infusion over 30 minutes, and the same cats received 100 mg of the drug orally 16 weeks later. The cats were bled repeatedly through an indwelling jugular catheter, the plasma fluconazole concentrations were assayed by high performance liquid chromatography, and the concentration-time data were subjected to a non-compartmental pharmacokinetic analysis. The mean (SD) intravenous half-life (13·8 [2·6] hours) was similar to that observed after oral dosing (12·4 [3·0] hours). The plasma clearances (intravenous 0·9 [0·1], oral 0·9 [0·2] ml min⁻¹ kg⁻¹) and the volumes of distribution at steady state (intravenous 1·1 [0·1], oral 1·0 [0·1] litre kg⁻¹) were also similar after the two routes of dosing. The peak plasma concentration was reached 2·6 hours after oral dosing and the drug was completely bioavailable (1·09 [0·05]). On the basis of this single dose study, the administration of 50 mg fluconazole every eight hours to a 4 kg cat should produce average steady state plasma fluconazole concentrations of approximately 33 mg litre⁻¹.     

Effect of stage of gestation and foetal number on plasma concentrations of a pregnancy serum protein (PSP-60) in cattle

This study characterised the peripheral plasma concentration of PSP-60 throughout gestation, and examined the effect of stage of gestation and foetal number on this protein in Holstein cows after non-surgical embryo transfer. Cows (n=12) were divided into two groups; Group 1 contained single embryo recipient cows (n=5), Group 2 contained twin-embryo recipient cows (n=7). Blood was collected approximately every third day from day 0 (first day of standing oestrus), then daily for the last 10 days of gestation and until one day post-partum. Two of the twin-embryo recipient cows had abnormal pregnancies, consequently data from them was considered separately. In both groups PSP-60 increased progressively from about day 20 post-oestrus to 20 days pre-partum (from 0·9 ± 0·2 to 49·7 ± 8·7 ng ml⁻¹, and from 1·3 ± 0·6 to 115 ± 34·9 ng ml⁻¹ (mean ± SEM), in singleton and twin-bearing groups, respectively). The mean concentrations between 20 and 10 days pre-partum increased dramatically by about six-fold (P<0·001) in singleton-bearing cows (from 49·7 ± 8·7 ng ml⁻¹ to 2838 ± 73·7 ng ml⁻¹) to over two-fold in twin-bearing cows (from 115 ± 34·9 ng ml⁻¹ to 284 ± 98·2 ng ml^-1). The mean concentrations of the two groups were indistinguishable between 10 days pre-parturn and parturition. Cows giving birth prematurely to stillborn calves or to a schistosomus reflexus calf exhibited abnormal PSP-60 profiles. Our findings indicate that peripheral plasma PSP-60 concentrations are correlated to the stage of gestation and foetal number, and assist in predicting foeto-placental viability.     

Bioavailability of transdermal methimazole in a pluronic lecithin organogel (PLO) in healthy cats

The antithyroid drug methimazole is widely used for the medical management of feline hyperthyroidism. Recently, custom veterinary pharmacies have offered methimazole in a transdermal gel containing pluronic and lecithin (PLO), with anecdotal evidence of efficacy. The purpose of this study was to determine the bioavailability, relative to i.v. and oral routes of administration, of transdermal methimazole in a PLO gel in cats. Six healthy adult cats were assigned to receive 5 mg of methimazole by the i.v., oral, or transdermal routes, in a randomized triple crossover protocol with 1 week washout between doses. Blood samples were taken for high performance liquid chromatography (HPLC) determination of serum methimazole, at 0, 5, 15, 30, 60 min, and 2, 4, 6, 12 and 24 h after dosing. Methimazole absorption following transdermal administration was poor and variable, with only two of six cats achieving detectable serum methimazole concentrations at any time point following transdermal administration. Area under the concentration-time curve (AUC), maximum concentration (Cmax), and absolute bioavailability were all significantly lower for the transdermal route (0.39 +/- 0.63 microg h/mL, 0.05 +/- 0.09 microg/mL, and 11.4 +/- 18.7%, respectively) than for either i.v. (7.96 +/- 4.38 microg h/mL, 3.34 +/- 2.00 microg/mL, 100%) or oral routes (2.94 +/- 1.24 microg h/mL, 0.51 +/- 0.15 microg/mL, 40.4 +/- 8.1%). The results of this study indicate generally low to undetectable bioavailability of methimazole in a lecithin/pluronic gel given as a single transdermal dose to healthy cats, although one individual cat did achieve nearly 100% transdermal bioavailability relative to the oral route.     

Transdermal carbimazole for the treatment of feline hyperthyroidism

Orally administered antithyroid drugs are frequently used to treat hyperthyroidism in cats; however, the non-cooperative behaviour of some cats may make it difficult to administer tablets. The aim of this study was to develop a carbimazole ointment for application to the inner pinna of the ear and to test its effectiveness in 13 cats with hyperthyroidism. Laboratory investigations were performed before, and 4, 8, and 12 weeks after start of the treatment. Laboratory data for 9 cats were available at the end of the observation period. The starting dose of carbimazole ointment was 5 mg once daily. If no complications occurred, the dose was increased to 5 mg twice daily from the 6th day onwards. Further dose adjustments were mainly based on the plasma thyroxine (T4) concentration. The median plasma T4 concentration at the end of the observation period (24 nmol/l) was significantly lower than that before treatment (152 nmol/l). The dosage of carbimazole needed to achieve euthyroidism ranged from 4 to 17 mg twice daily. Treatment with carbimazole ointment resulted in disappearance of signs of hyperthyroidism; plasma concentrations of urea and creatinine increased significantly. The results of this study indicate that twice daily administration of carbimazole ointment to the inner pinna of the ear is an effective treatment for hyperthyroidism in cats. This provides the veterinarian with a new and promising treatment option. Because carbimazole ointment has not been registered, according to European law it can only be used for the treatment of hyperthyroidism in cats if other licensed medications have been tried and if there is a therapeutic need.     

Lincomycin and spectinomycin in the treatment of breeding rams with semen contaminated with ureaplasmas

Ureaplasma species were isolated from semen samples collected sequentially from one Awassi and three Assaf breeding rams. Each ram was injected subcutaneously with an aqueous solution of lincomycin and spectinomycin for five consecutive days at a dose equivalent to 4·5 mg kg⁻¹ lincomycin and 9·0 mg kg⁻¹ spectinomycin daily. Serum and semen samples were collected at intervals during the treatment and assayed for lincomycin. No Ureaplasma species were isolated from semen samples collected during the course of the treatment and at intervals for 17 days after the last treatment. The concentration of lincomycin in semen ranged from 0·51 μg ml⁻¹ four hours after treatment to 0·08 μg ml⁻¹ 24 hours after treatment, and these levels were three to nine times higher than the corresponding serum concentrations.     

Influence on the antithyroid compound methimazole on the plasma disposition of fenbendazole and oxfendazole in sheep

The influence of methimazole on the plasma disposition kinetics of fenbendazole, oxfendazole and their metabolites, was investigated in adult sheep. The two anthelmintics were administered by oral drench at 5 mg kg⁻¹ either alone (control treatments) or together with methimazole given orally at 3 mg kg⁻¹. Blood samples were taken serially for 144 hours. Fenbendazole parent drug and its sulphoxide and sulphone metabolites were the three analytes observed by high performance liquid chromatography ( ) after the administration of both anthelmintics. The disposition of each analyte followed a similar pattern after the administration of the two anthehnintics alone. Oxfendazole was the main component recovered in plasma between four and 120 to 144 hours after the administration of both anthelmintics either with or without methimazole. A modified pattern of disposition, with significantly higher C_max and values for fenbendazole parent drug, and a delayed appearance in plasma with retarded T_max values for the sulphoxide and sulphone metabolites, were the main pharmacokinetic changes observed when the drugs were administered with methimazole.     

Best practice for the pharmacological management of hyperthyroid cats with antithyroid drugs

Pharmacological management of feline hyperthyroidism offers a practical treatment option for many hyperthyroid cats. Two drugs have been licensed for cats in the last decade: methimazole and its pro‐drug carbimazole. On the basis of current evidence and available tablet sizes, starting doses of 2·5 mg methimazole twice a day and 10 to 15 mg once a day for the sustained release formulation of carbimazole are recommended. These doses should then be titrated to effect in order to obtain circulating total thyroxine (TT4) concentrations in the lower half of the reference interval. Treated cases should be monitored for side‐effects, especially during the first months of treatment. Some side‐effects may require discontinuation of treatment. At each monitoring visit, clinical condition and quality of life should also be evaluated, with special attention to possible development of azotaemia, hypertension and iatrogenic hypothyroidism. When euthyroidism has been achieved, monitoring visits are recommended after 1 month, 3 months and biannually thereafter. Cats with pre‐existing azotaemia have shorter survival times. However, development of mild azotaemia during the initial course of treatment, unless associated with hypothyroidism, does not appear to decrease survival time. The long‐term effects of chronic medical management require further study .     

Percutaneous absorption of methimazole: an in vitro study of the absorption pharmacokinetics for two different vehicles

The use of transdermal medications in cats has become popular in veterinary medicine due to the ease of administration compared to oral medication. However, the research to support systemic absorption of drugs applied to the pinna after transdermal administration in cats is limited. The aim of this study was to characterize the percutaneous absorption pharmacokinetics of methimazole in a lipophilic vehicle compared to methimazole in Pluronic^® lecithin organogel (PLO) using a finite dose applied to feline ear skin in an in vitro Franz cell model. The two formulations of methimazole (10 mg) were applied to the inner stratum corneum of six pairs of feline ears. The receptor medium was sampled up to 30 h post–administration, and methimazole concentrations were measured using high‐performance liquid chromatography (HPLC). Histological examination of all ears was undertaken as small differences in the thickness of ear skin may have contributed to inter‐individual differences in methimazole absorption between six cats. Methimazole was absorbed more completely across the pinnal skin when administered in the lipophilic vehicle compared to administration in the PLO gel (P < 0.001).     

Methimazole Treatment of 262 Cats With Hyperthyroidism

The efficacy and safety of the antithyroid drug methimazole were evaluated over a 3-year period in 262 cats with hyperthyroidism. In 181 of the cats, methimazole was administered for 7 to 130 days (mean, 27.7 days) as a preoperative preparation for thyroidectomy. The remaining 81 cats were given methimazole for 30 to 1,000 days (mean, 228 days) as sole treatment for the hyperthyroid state. After 2 to 3 weeks of methimazole therapy (10 to 15 mg/d), the mean serum thyroxine (T4) concentration decreased significantly (P less than 0.001) from a pretreatment value of 12.1 micrograms/dl to 2.1 micrograms/dl. The final maintenance dose needed to maintain euthyroidism in the 81 cats that were given methimazole as sole treatment for hyperthyroidism ranged from 2.5 to 20 mg/d (mean, 11.9 mg/d). Clinical side effects developed in 48 (18.3%) cats (usually within the first month of therapy), which included anorexia, vomiting, lethargy, self-induced excoriation of the face and neck, bleeding diathesis, and icterus caused by hepatopathy. Mild hematologic abnormalities developed in 43 (16.4%) cats (usually within the first 2 months of treatment), which included eosinophilia, lymphocytosis, and slight leukopenia. In ten (3.8%) cats, more serious hematologic reactions developed including agranulocytosis and thrombocytopenia (associated with bleeding). These hematologic abnormalities resolved within 1 week after cessation of methimazole treatment. Immunologic abnormalities associated with methimazole treatment included the development of antinuclear antibodies in 52 of 238 (21.8%) cats tested and red cell autoantibodies (as evidenced by positive direct antiglobulin tests) in three of 160 (1.9%) cats tested.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of intravenous and oral methimazole following single-and multiple-dose administration in normal cats

The pharmacokinetics of methimazole (MMI) administered intravenously and orally were determined in six adult domestic shorthaired cats. There was no significant difference between mean serum MMI concentrations after oral and i.v. administration by 30 min post-MMI administration, indicating relatively rapid and complete absorption of the drug. The bioavailability of MMI ranged from 27% to 100% (mean = 81.1 +/- 11.4%). The mean serum elimination half-life was 6.6 +/- 2.0 h, with a wide range of values (1.9 h to 15.1 h). After repeat i.v. administration of MMI following 2 weeks of oral administration of the drug, no significant difference was found between mean serum concentrations after single-dose and multiple-dose administration. No significant change in serum elimination half-life or total body clearance was found after multiple-dose administration of MMI. Two cats with the longest half-lives (9.9 h and 15.1 h), however, did exhibit markedly shorter t1/2 values (3.5 h and 3.3 h, respectively) after multiple-dose administration. Values for central and steady state volumes of distribution also decreased after multiple-dose administration, possibly indicating saturation of thyroid uptake of MMI with chronic administration. These results indicate that MMI has good oral bioavailability and has a longer mean serum elimination half-life than propylthiouracil, the other anti-thyroid drug that has been evaluated in cats. Although no significant change in mean values occurred after multiple-dose administration of MMI, drug-induced acceleration of metabolism may occur in some cats after long-term MMI administration.     

THE EFFECT OF METHIMAZOLE ON THYROID UPTAKE OF PERTECHNETATE AND RADIOIODINE IN NORMAL CATS

Many hyperthyroid cats referred for thyroid imaging and 131I therapy are concurrently or recently receiving antithyroid medications. The effect of the antithyroid drug, methimazole, on thyroid uptake of 99mTcO4 and 123I was evaluated in 8 normal cats. Quantitative analysis was used to determine the normal percent dose uptake of 99mTcO4 and 123I, the change in thyroid:salivary ratios (T:S) of 99-TcO4 over time, and the duration of the methimazole effect on thyroid uptake of 123I. Methimazole was administered to 5 cats for 3 weeks in which a hypothyroid state was obtained; 3 cats served as non-treatment controls. 99mTcO4 and 8 and 24 hour 123I imaging was repeated after 3 weeks of methimazole therapy (time of maximum T4 suppression). Methimazole was then discontinued and 123I images and serum T4 concentrations were repeated at 1, 4, 9, 15, and 24 days post withdrawal. The percent dose uptake of 99mTcO4 increased throughout the acquisition period with maximum uptake occurring 4 hour post injection. The baseline 20 min. T:S ratio for controls and treatment cats were 0.79 +/- 0.08 and 0.81 +/- 0.05 respectively; with a peak value of 1.29 +/- 0.23 and 1.31 +/- 0.18 at 4 hours. The baseline T:S ratios were not significantly different from 20 minutes to 2 hours, however they were significantly elevated at 4 hours post injection. Baseline, 8 and 24 hour percent dose uptake of 123I were 2.1 +/- 0.42% and 7.04 +/- 1.24%, respectively. There was a significant increase in the T:S ratio in the treatment group at all time points. The 8 hour percent dose uptake of 123I at 1, 4, and 9 days post methimazole withdrawal were significantly increased and peaked at 4 days. The 24 hour uptake was significantly increased at 4 and 9 days, with peak uptake at 9 days post-methimazole withdrawal. The 123I percent dose uptake decreased to baseline values by day 15 post withdrawal. Radioiodine uptake is not inhibited by methimazole treatment in normal cats, and is significantly enhanced after recent withdrawal. This finding is supportive of a "short term rebund effect" with maximal enhanced uptake between 4 and 9 days after discontinuing antithyroid drugs. The increased uptake of 99mTcO4 may also affect the interpretation of 99mTcO4 thyroid scintigraphy for 2-3 weeks.     

Effects of inhibition of nitric oxide synthase on systemic arterial pressure and renal vascular resistance in cats

These studies were undertaken to examine the systemic and renal effects of the pharmacological inhibition of endothelium-derived nitric oxide (EDNO) in cats. In six healthy cats, the intravenous infusion of nitro-L-arginine at a dose of 100 μg kg⁻¹ bodyweight min⁻¹ resulted in a marked increase (P<0·001) in mean arterial pressure from the control value of 116·7 ± 4·6 mmHg to 154·2 ± 6·8 mmHg and an increase (P<0·05) in renal vascular resistance from the control value of 3·69 ± 0·33 mmHg min ml⁻¹ to 6·83 ± 1·15 mmHg min ml⁻¹. The increase in renal vascular resistance was generalised, with comparable increments in preglomerular and postglomerular vascular resistance. Mean values for glomerular capillary pressure (61·1 ± 61·9 vs 1·9 ± 1·6 mmHg), calculated from the sum of arterial colloid osmotic pressure plus proximal tubule stop-flow pressure, did not change in response to the infusion of nitro-L-arginine. However, there was a marked reduction in renal blood flow (29·4 ± 3·1 to 16·9 ± 2·3 ml min⁻¹, P<0·01) and glomerular filtration rate (5·22 ± 0·57 to 3·52 ± 0·45 ml min⁻¹, P<0·01). These results provide evidence that EDNO plays an important role in the basal regulation of systemic arterial blood pressure and renal haemodynamics in cats.     

Evaluation of free and liposome-encapsulated gentamycin for intramuscular sustained release in rabbits

Gentamycin sulphate ( ) and gentamycin oleate ( ) were encapsulated in liposomes composed of phosphatidylcholine ( ) and cholesterol ( ) (molar ratio 7:7:2 and 5:5:l, respectively), and were administered via intramuscular injection to rabbits, to evaluate their potential use as sustained release formulations. Five groups of five animals each were used for the pharmacokinetic study, and treatments were established as follows: 3 mg kg⁻¹ of i.v., 3 mg kg⁻¹ of i.m., 3 mg kg⁻¹ of liposome-containing gentamycin sulphate ( ) i.m., 3 mg kg⁻¹ of i.m., and 3 mg kg⁻¹ of liposome-containing gentamycin oleate ( ) i.m. Gentamycin plasma concentrations after i.m. administration of LGS were extremely low compared with those obtained after the i.m. administration of ; the peak plasma concentration ( _max) showed an eight-fold decrease with , and the area under the concentration-time curve ( ) was four-fold lower for the liposomal form. The apparent elimination half-life estimated after administration of showed a three-fold increase compared with values calculated for free . After the administration of the same dose of , _max obtained showed a 2·5-fold decrease in relation to peak concentrations of free , and the apparent β-half life of encapsulated showed a three-fold increase compared with i.m. . Large-size liposomes containing gentamycin administered i.m. to rabbits gave sustained drug release from the injection site, providing prolonged plasma concentrations of the drug in the body.     

Pharmacokinetics of isavuconazole in healthy cats after oral and intravenous administration

BackgroundIsavuconazole is a triazole antifungal drug that has shown good efficacy in human patients. Absorption and pharmacokinetics have not been evaluated in cats.ObjectivesTo determine the pharmacokinetics of isavuconazole in cats given a single IV or PO dose.AnimalsEight healthy, adult research cats.MethodsFour cats received 100 mg capsules of isavuconazole PO. Four cats received 5 mg/kg isavuconazole solution IV. Serum was collected at predetermined intervals for analysis using ultra‐high performance liquid chromatography‐tandem mass spectrometry. Data were analyzed using a 2‐compartment uniform weighting pharmacokinetic analysis with lag time for PO administration and a 2 compartment, 1/y² weighting for IV administration. Predicted 24 and 48‐hour dosing intervals of 100 mg isavuconazole administered PO were modeled and in vitro plasma protein binding was assessed.ResultsBoth PO and IV drug administration resulted in high serum concentrations. Intravenous and PO formulations of isavuconazole appear to be able to be used interchangeably. Peak serum isavuconazole concentrations occurred 5 ± 3.8 hours after PO administration with an elimination rate half‐life of 66.2 ± 55.3 hours. Intersubject variability was apparent in both the PO and IV groups. Two cats vomited 6 to 8 hours after PO administration. No adverse effects were observed in the IV group. Oral bioavailability was estimated to be approximately 88%. Serum protein binding was calculated to be approximately 99.0% ± 0.03%.Conclusions and Clinical ImportanceIsavuconazole might prove to be useful in cats with fungal disease given its favorable pharmacokinetics. Additional studies on safety, efficacy, and tolerability of long‐term isavuconazole use are needed.     

Optimal Testing for Thyroid Hormone Concentration after Treatment with Methimazole in Healthy and Hyperthyroid Cats

Background: Methimazole suppresses thyroid hormone synthesis and is commonly used to treat feline hyperthyroidism. The degree of variation in thyroid hormone concentrations 24 hours after administration of methimazole and optimal time for blood sampling to monitor therapeutic efficacy have not been determined.
Objective: To assess thyroid hormone concentration variation in serum of normal and hyperthyroid cats after administration of methimazole.
Animals: Four healthy cats and 889 retrospectively acquired feline thyroid hormone profiles.
Methods: Crossover and retrospective studies . In the crossover study, healthy cats were treated with increasing doses of oral methimazole until steady state of thyroid suppression was achieved. Thyroid hormones and thyroid stimulating hormone (TSH) were serially and randomly monitored after methimazole. Paired t -tests and a 3-factor analysis of variance were used to determine differences between thyroid hormone concentrations in treated and untreated cats in the crossover study. Thyroid profiles from methimazole-treated hyperthyroid cats were retrieved from the Diagnostic Center for Population and Animal Health database and reviewed. Linear regression analysis evaluated relationships of dosage (mg/kg), dosing interval (q24h versus q12h), and time after methimazole to all thyroid hormone concentrations.
Results: All serum concentrations of thyroid hormones were significantly suppressed and TSH was significantly increased for 24 hours after administration of oral methimazole in healthy cats ( P < .005). In hyperthyroid cats, there were no significant relationships between thyroid hormone concentrations and time postpill or dosing interval.
Conclusions: Timing of blood sampling after oral methimazole administration does not appear to be a significant factor when assessing response to methimazole treatment.     

Effect of dietary chloride content on the elimination of bromide by dogs

The effect of dietary chloride content (0·2, 0·4 and 1·3 per cent chloride on a dry matter basis) on the disposition of a single oral dose of bromide (14 mg kg⁻¹ was evaluated in normal beagles. Increasing the dietary chloride content from 0·2 to 1·3 per cent resulted in a significant decrease in the mean apparent elimination half-life from 69 ± 22 days to 24 ± 7 days. The mean area under the concentration curve ( ) for dogs fed 1·3 per cent chloride was significantly smaller than the for dogs fed 0·2 per cent chloride. Dietary chloride had no effect on the maximum serum concentrations (C_max) or on the time (T_max) to reach the maximum concentrations. The steady-state serum bromide concentrations predicted from the single dose data for daily doses of 14 mg kg⁻¹ of bromide were significantly lower in dogs fed 1·3 per cent chloride (310 ± 150 mg litre⁻¹) than in dogs fed 0·2 per cent chloride (1950 ± 1140 mg litre⁻¹). The predicted mean daily doses of bromide necessary to maintain serum levels within the therapeutic range for dogs fed 1·3 per cent chloride (43 ± 13 mg kg⁻¹) were almost twice as high as the dose estimated for dogs fed 0·4 per cent chloride (22 ± 3 mg kg⁻¹) and nearly three times as high as the dose estimated for dogs fed 0·2 per cent chloride (15 ± 4 mg kg^−l). These differences were statistically significant (P=0·002).     

Serum troponin T concentrations in two strains of commercial broiler chickens aged one to 56 days

Troponin T is a specific and sensitive serological indicator of acute myocardial infarction in human patients. The concentration of serum troponin T was measured by an technique in two strains of healthy commercial broiler chickens (Cobb 500 and Ross I) aged between one and 56 days. The concentrations of cardiac-derived troponin T in day-old Cobb and Ross chicks were 5·74 and 8·35 ng ml⁻¹, respectively, and much higher than in 14-day-old chicks. Between 21 and 56 days, the values were consistently lower than the mean troponin T concentration of 0·20 ng ml⁻¹ reported previously in a group of healthy 30-day-old broilers. All the other heart measurements, including the arterial pressure index, were within normal limits. The high troponin T concentrations after hatching are probably due to an embryonic isoform that rapidly becomes replaced by an adult isoform by three weeks of age. The data suggest that in healthy birds, there is an inverse relationship between troponin T concentrations and age.     

Duration of T4 Suppression in Hyperthyroid Cats Treated Once and Twice Daily with Transdermal Methimazole

Background

Transdermal methimazole is an acceptable alternative to oral treatment for hyperthyroid cats. There are, however, no studies evaluating the duration of T4 suppression after transdermal methimazole application. Such information would be valuable for therapeutic monitoring.

Objective

To assess variation in serum T4 concentration in hyperthyroid cats after once‐ and twice‐daily transdermal methimazole administration.

Animals

Twenty client‐owned cats with newly diagnosed hyperthyroidism.

Methods

Methimazole was formulated in a pluronic lecithin organogel‐based vehicle and applied to the pinna of the inner ear at a starting dose of 2.5 mg/cat q12h (BID group, 10 cats) and 5 mg/cat q24h (SID group, 10 cats). One and 3 weeks after starting treatment, T4 concentrations were measured immediately before and every 2 hours after gel application over a period of up to 10 hours.

Results

Significantly decreased T4 concentrations were observed in week 1 and 3 compared with pretreatment concentrations in both groups. All cats showed sustained suppression of T4 concentration during the 10‐hour period, and T4 concentrations immediately before the next methimazole treatment were not significantly different compared with any time point after application, either in the BID or SID groups.

Conclusions

Because transdermal methimazole application led to prolonged T4 suppression in both the BID and SID groups, timing of blood sampling does not seem to be critical when assessing treatment response.