Evaluation of extended-release diltiazem once daily for cats with hypertrophic cardiomyopathy

Serum diltiazem concentrations were evaluated following either 30 mg or 60 mg of an extended-release diltiazem administered orally once daily to 13 cats. Sequential blood samples were obtained over 24 hours. Both dosages usually resulted in elevated serum concentrations of >200 ng/mL at 6, 12, 18, and 24 hours. The 30-mg dosage was sometimes associated with low serum concentrations of <50 ng/mL at 18 and 24 hours. The 60-mg dosage (9.3 to 14.8 mg/kg) was associated with lethargy, gastrointestinal disturbances, and weight loss in nine (36%) of 25 client-owned cats. Gastrointestinal disturbances were recognized within 1 week, and weight loss was detected after 2 to 6 months of treatment.     

Serum concentrations of methimazole in cats after a single oral dose of controlled-release carbimazole or sugar-coated methimazole (thiamazole)

In the past 5 years, the incidence of canine skin infections caused by resistant strains of Staphylococcus (pseud)intermedius has increased. Many older antibiotics are used to treat these infections because the sensitivity can be demonstrated in vitro. Additionally, many of these older drugs are efficacious and unlikely to induce multidrug resistance. More than a decade ago, the antibiotic tylosin tartrate was reported to be efficacious in vitro and in vivo against Staphylococcus intermedius. The purpose of this study was to determine whether S. (pseud)intermedius isolated from untreated pyoderma cases at veterinary referral centers across the United States are sensitive in vitro to this antibiotic. Minimum inhibitory concentrations for tylosin tartrate and other commonly used antibiotics were determined for 103 isolates. Most (82.61%) of the isolates not exposed to antibiotics in the 3 months before submission were sensitive to tylosin tartrate. These findings suggest that tylosin tartrate warrants further study as a first-line option for the treatment of dogs initially presenting with pyoderma.     

Efficacy and safety of once versus twice daily administration of methimazole in cats with hyperthyroidism

OBJECTIVE: To determine whether once daily administration of methimazole was as effective and safe as twice daily administration in cats with hyperthyroidism. DESIGN: Randomized, nonblinded, clinical trial. ANIMALS: 40 cats with newly diagnosed hyperthyroidism. PROCEDURE: Cats were randomly assigned to receive 5 mg of methimazole, PO, once daily (n = 25) or 2.5 mg of methimazole, PO, twice daily (15). A complete physical examination, including measurement of body weight; CBC; serum biochemical analyses, including measurement of serum thyroxine concentration; and urinalysis were performed, and blood pressure was measured before and 2 and 4 weeks after initiation of treatment. RESULTS: Serum thyroxine concentration was significantly higher in cats given methimazole once daily, compared with cats given methimazole twice daily, 2 weeks (3.7 vs 2.0 micro +/- g/dL) and 4 weeks (3.2 vs 1.7 microg/dL) after initiation of treatment. In addition, the proportion of cats that were euthyroid after 2 weeks of treatment was lower for cats receiving methimazole once daily (54%) than for cats receiving methimazole twice daily (87%). Percentages of cats with adverse effects (primarily gastrointestinal tract upset and facial pruritus) were not significantly different between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that once daily administration of methimazole was not as effective as twice daily administration in cats with hyperthyroidism and cannot be recommended for routine use.     

Insulin glargine has a long duration of effect following administration either once daily or twice daily in divided doses in healthy cats

The pharmacological effects of glargine administered once or twice daily were compared in six healthy cats. A two-way crossover study was performed with insulin and glucose concentrations measured following subcutaneous administration of glargine once daily (0.5U/kg) or twice daily (0.25U/kg, repeated after 12h). Nadir glucose concentration and mean daily glucose concentration did not differ significantly following insulin administration once daily or twice daily in divided doses. Time to reach last glucose nadir differed, with longer intervals occurring following twice daily dosing. Blood glucose failed to return to baseline concentration by 24h in three of six cats in each treatment group. Insulin variables were not significantly different following once or twice daily dosing. This study in healthy cats demonstrates that glargine has a long duration of action with carry-over effects to the next day likely, regardless of dosing regimen. A study in diabetic cats is required to determine the best dosing regimen.     

Comparison of the disposition of carbimazole and methimazole in clinically normal cats

The oral disposition of the antithyroid drugs methimazole and carbimazole were compared in nine clinically normal cats. After the administration of 5 mg of methimazole, serum concentrations of methimazole increased in all the cats, with mean drug concentrations reaching peak values (1·37 μg ml⁻¹) at 30 minutes. After administration of 5 mg carbimazole, serum concentrations of carbimazole remained low, but serum methnnazole became readily measurable, with mean drug concentrations reaching peak values (0·79 μg ml⁻¹) at 120 minutes. When serum concentrations of methimazole attained after administration of the two antithyroid drugs were compared, the mean maximum serum methimazole concentration achieved after administration of methimazole was approximately two-fold higher than peak concentrations measured after administration of carbimazole. In addition, the mean area under the serum concentration curve (AUC) after administration of methimazole was approximately two-fold higher than the mean AUC determined after administration of carbimazole. When the differences in molecular weight between the two drugs was taken into consideration, however, these methimazole:carbimazole ratios of 2:1 were nearly equivalent to the molar ratio of the 5 mg doses of the drugs given (1·63). Results of this study indicate that carbimazole is nearly totally converted to methimazole after oral administration to cats, similarly to the findings in man. The finding of less available serum methimazole after administration of a 5 mg tablet of carbimazole than after methimazole is also consistent with published antithyroid drug dosages needed to control hyperthyroidism in cats.     

Pharmacokinetics of masitinib in cats

Masitinib is the first veterinary drug recently approved in Europe to treat mast cell tumours in dogs (Hahn et al. JVIM, Masivet). This inhibitor is selective and highly efficient in blocking c-Kit, PDGFR, and Lyn tyrosine kinase activities. It showed good efficacy and acceptable toxicity in several animal studies such as mice, rats, rabbits and dogs (Dubreuil P, et al. submitted, and Hahn et al. (J Vet Intern Med 22(6):8, 2008)). C-kit is a tyrosine kinase receptor that plays a critical role in the biology of mast cells including differentiation, survival, migration and cytokine/mediator release. Mast cells are involved in a number of allergy-and immune-related diseases in cats such as asthma (Reinero Carol et al. Vet Immunol Immunopathol 121(3–4):9, 2008), inflammatory bowel disease, (Janeczko et al. Vet Mic 128(1–2):15, 2008), and feline mast cell tumours (Rassnick et al. J Am Vet Med Assoc 232(8):1200–1205, 2008). Therefore, there might be a strong rationale to use masitinib in these indications. Here, we report the results of a preliminary pharmacokinetic study of masitinib in cats which showed a good bioavailability of ~60% in both sexes. We propose that an oral dose of 10–15 mg/kg masitinib is appropriate to achieve adequate plasma concentrations.     

Pharmacokinetics of etomidate in cats

Pharmacokinetic variables of etomidate were determined after IV administration of etomidate (3.0 mg/kg of body weight). Blood samples were collected for 6 hours. Disposition of this carboxylated imidazole best conformed to a 2- (n = 2) and a 3- compartment (n = 4) open pharmacokinetic model. The pharmacokinetic values were calculated for the overall best-fitted model, characterized as a mixed 2- and 3-compartmental model. The first and most rapid distribution half-life was 0.05 hour and a second distribution half-life was 0.35 hour. Elimination half-life was 2.89 hours, apparent volume of distribution was 11.87 +/- 4.64 L/kg, apparent volume of distribution at steady state was 4.88 +/- 2.25 L/kg, apparent volume of the central compartment was 1.17 +/- 0.70 L/kg, and total clearance was 2.47 +/- 0.78 L/kg/h.     

Pharmacokinetics of cefovecin in cats

The pharmacokinetics of the novel cephalosporin cefovecin were investigated in a series of in vivo, ex vivo and in vitro studies following administration to adult cats at 8 mg/kg bodyweight. Bioavailability and pharmacokinetic parameters were determined in a cross-over study after intravenous (i.v.) and subcutaneous (s.c.) injections. [14C]cefovecin was used to evaluate excretion for 21 days after s.c. administration. Protein binding was determined in vitro in feline plasma and ex vivo in transudate from cats surgically implanted with tissue chambers. After s.c. administration, cefovecin was characterized by rapid absorption with mean peak plasma concentrations of 141+/-12 microg/mL being achieved within 2 h of s.c. injection with full bioavailability (99%). The mean elimination half-life was 166+/-18 h. After i.v. administration, volume of distribution was 0.09+/-0.01 L/kg and mean plasma clearance was 0.35+/-0.04 mL/h/kg. Approximately 50% of the administered radiolabelled dose was eliminated over the 21-day postdose period via urinary excretion and up to approximately 25% in faeces. In vitro and ex vivo plasma protein binding ranged from 99.8% to 99.5% over the plasma concentration range 10-100 microg/mL. Ex vivo protein binding in transudate was as low as 90.7%. From 8 h postdose, concentrations of unbound (free) cefovecin in transudate were consistently higher than in plasma, with mean unbound cefovecin concentrations being maintained above 0.06 microg/mL (MIC90 of Pasteurella multocida) in transudate for at least 14 days postdose. The slow elimination and long-lasting free concentrations in extracellular fluid are desirable pharmacokinetic attributes for an antimicrobial with a 14-day dosing interval.     

Pharmacokinetics of amikacin in cats

Six mixed-breed adult cats were given 5 mg of amikacin sulfate/kg of body weight by rapid IV, IM, and SC routes of administration. The serum concentration-vs-time data were analyzed, using a noncompartmental model. The harmonic mean +/- pseudo-SD of the effective half-life of amikacin was 78.8 +/- 19.3 minutes after IV administration, 118.7 +/- 14.4 minutes after IM administration, and 117.7 +/- 12.8 minutes after SC administration. The arithmetic mean +/- SD of mean residence time was 118.3 +/- 21.7 minutes, 173.4 +/- 19.9 minutes, and 171.7 +/- 19.1 minutes after IV, IM, and SC drug administration, respectively. The mean apparent volume of distribution at steady state was 0.17 +/- 0.02 L/kg, and the mean total body clearance was 1.46 +/- 0.26 ml/min/kg. Mean bioavailability was 95 +/- 20% after IM administration and 123 +/- 33% after SC drug administration. A recommended dosage of 10 mg/kg, q 8 h can be expected to provide a therapeutic serum concentration of amikacin with a mean steady-state concentration of 14 micrograms/ml. The SC route of administration is preferred, because of rapid absorption, good bioavailability, and ease of administration.     

Pharmacokinetics of amantadine in cats

Siao, K. T., Pypendop, B. H., Stanley, S. D., Ilkiw, J. E. Pharmacokinetics of amantadine in cats. J. vet. Pharmacol. Therap. 34 , 599–604. This study reports the pharmacokinetics of amantadine in cats, after both i.v. and oral administration. Six healthy adult domestic shorthair female cats were used. Amantadine HCl (5 mg/kg, equivalent to 4 mg/kg amantadine base) was administered either intravenously or orally in a crossover randomized design. Blood samples were collected immediately prior to amantadine administration, and at various times up to 1440 min following intravenous, or up to 2880 min following oral administration. Plasma amantadine concentrations were determined by liquid chromatography–mass spectrometry, and plasma amantadine concentration–time data were fitted to compartmental models. A two‐compartment model with elimination from the central compartment best described the disposition of amantadine administered intravenously in cats, and a one‐compartment model best described the disposition of oral amantadine in cats. After i.v. administration, the apparent volume of distribution of the central compartment and apparent volume of distribution at steady‐state [mean ± SEM (range)], and the clearance and terminal half‐life [harmonic mean ± jackknife pseudo‐SD (range)] were 1.5 ± 0.3 (0.7–2.5) L/kg, 4.3 ± 0.2 (3.7–5.0) L/kg, 8.2 ± 2.1 (5.9–11.4) mL·min/kg, and 348 ± 49 (307–465) min, respectively. Systemic availability [mean ± SEM (range)] and terminal half‐life after oral administration [harmonic mean ± jackknife pseudo‐SD (range)] were 130 ± 11 (86–160)% and 324 ± 41 (277–381) min, respectively.     

Pharmacokinetics of thiamylal in cats

Pharmacokinetics of thiamylal were determined after 13.2 mg of thiamylal/kg of body weight was administered IV to 6 healthy cats. Blood samples were obtained for 12 hours. Disposition of thiamylal best conformed to 2 multicompartmental models, a 2-compartment (n = 1) and a 3-compartment (n = 5) open pharmacokinetic model. The pharmacokinetic values were calculated for the overall best-fitted model, a mixed 2- and 3-compartmental model. The first or rapid distribution half-life was 1.91 minutes and a second, or slower, distribution half-life was 26.51 minutes. The elimination half-life was 14.34 hours. The apparent volume of distribution was 3.61 +/- 1.8463 L/kg, whereas the apparent volume of the central compartment was 0.46 +/- 0.2034 L/kg, and the total clearance was 0.135 +/- 0.0616 L/kg/h.     

Pharmacokinetics of lamivudine in cats

OBJECTIVE: To characterize the pharmacokinetics of lamivudine (3TC) in cats. ANIMALS: 6 sexually intact 9-month-old barrier-reared domestic shorthair cats. PROCEDURE: Cats were randomly alloted into 3 groups, and lamivudine (25 mg/kg) was administered i.v., intragastrically (i.g.), and p.o. in a 3-way crossover study design with 2-week washout periods between experiments. Plasma samples were collected for 12 hours after drug administration, and lamivudine concentrations were determined by high-performance liquid chromatography. Maximum plasma concentrations (Cmax), time to reach Cmax (Tmax), and bioavailability were compared between i.g. and p.o. routes. Area under the curve (AUC) and terminal phase half-life (t(1/2)) among the 3 administration routes were also compared. RESULTS: Plasma concentrations of lamivudine declined rapidly with a t(1/2) of 1.9 +/- 0.21 hours, 2.6 +/- 0.66 hours, and 2.7 +/- 1.50 hours after i.v., i.g., and p.o. administration, respectively. Total body clearance and steady-state volume of distribution were 0.22 +/- 0.09 L/h/kg and 0.60 +/- 0.22 L/kg, respectively. Mean Tmax for i.g. administration (0.5 hours) was significantly shorter than Tmax for p.o. administration (1.1 hours). The AUC after i.v., i.g., and p.o. administration was 130 +/- 55.2 mg x h/L, 115 +/- 97.5 mg x h/L, and 106 +/- 94.9 mg x h/L, respectively. Lamivudine was well absorbed after i.g. and p.o. administration with bioavailability values of 88 +/- 45% and 80 +/- 52%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Cats had a shorter t(1/2) but slower total clearance of lamivudine, compared with humans. Plasma concentrations of lamivudine were maintained above the minimum effective concentration for inhibiting FIV replication by 50% (0.14 microM [0.032 microg/mL] for wild-type FIV clinical isolate) for at least 12 hours after i.v., i.g., or p.o. administration.     

Pharmacokinetics of oxymorphone in cats

Siao, K. T., Pypendop, B. H., Stanley, S. D., Ilkiw, J. E. Pharmacokinetics of oxymorphone in cats. J. vet. Pharmacol. Therap. 34 , 594–598. This study reports the pharmacokinetics of oxymorphone in spayed female cats after intravenous administration. Six healthy adult domestic shorthair spayed female cats were used. Oxymorphone (0.1 mg/kg) was administered intravenously as a bolus. Blood samples were collected immediately prior to oxymorphone administration and at various times up to 480 min following administration. Plasma oxymorphone concentrations were determined by liquid chromatography–mass spectrometry, and plasma oxymorphone concentration–time data were fitted to compartmental models. A three‐compartment model, with input in and elimination from the central compartment, best described the disposition of oxymorphone following intravenous administration. The apparent volume of distribution of the central compartment and apparent volume of distribution at steady state [mean ± SEM (range)] and the clearance and terminal half‐life [harmonic mean ± jackknife pseudo‐SD (range)] were 1.1 ± 0.2 (0.4–1.7) L/kg, 2.5 ± 0.4 (2.4–4.4) L/kg, 26 ± 7 (18–38) mL/min.kg, and 96 ± 49 (62–277) min, respectively. The disposition of oxymorphone in cats is characterized by a moderate volume of distribution and a short terminal half‐life.     

Pharmacokinetics of tobramycin in cats

Tobramycin was administered to cats and its serum concentration vs time data were analyzed by use of a noncompartmental model. In the first experiment, 5 mg of tobramycin/kg of body weight was administered IV, IM, and then SC to 6 cats, 3 weeks apart. After IV administration, the mean +/- SD total body clearance of tobramycin was 2.21 +/- 0.59 ml/min/kg, and the apparent volume of distribution at steady state was 0.19 +/- 0.03 L/kg. The mean residence time was 90.5 +/- 16.2 minutes, with a harmonic mean serum half-life of 68.9 +/- 9.7 minutes. Blood urea nitrogen and serum creatinine concentrations were increased 3 weeks after the IV injection and also 3 weeks after the IM injection, which suggested possible renal damage. Moreover, large area under the curve values developed after IM and SC administrations, resulting in bioavailabilities of 159.5% and 189.9%, respectively, with no change in elimination rate. These results suggested a change in distribution, possibly caused by saturation of renal binding sites by residual tobramycin from the previous injection of 5 mg/kg. In experiment 2, 6 other cats were given 3 mg of tobramycin/kg by the same routes as before, but using a crossover design. Bioavailability after IM and SC administrations was 102.5% and 99.2%, respectively, indicating complete absorption of tobramycin. The BUN concentration increased in 3 cats, and serum creatinine concentration increased in 1 of these 3 cats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of zidovudine in cats

OBJECTIVE: To characterize the pharmacokinetics of zidovudine (AZT) in cats. ANIMALS: 6 sexually intact 9-month-old barrier-reared domestic shorthair cats. PROCEDURE: Cats were randomly alloted into 3 groups, and zidovudine (25 mg/kg) was administered i.v., intragastrically (i.g.), and p.o. in a 3-way crossover study design with 2-week washout periods between experiments. Plasma samples were collected for 12 hours after drug administration, and zidovudine concentrations were determined by high-performance liquid chromatography. Maximum plasma concentrations (Cmax), time to reach Cmax (Tmax), and bioavailability were compared between i.g. and p.o. routes. Area under the curve (AUC) and terminal phase half-life (t(1/2)) among the 3 administration routes were also compared. RESULTS: Plasma concentrations of zidovudine declined rapidly with t(1/2) of 1.4 +/- 0.19 hours, 1.4 +/- 0.16 hours, and 1.5 +/- 0.28 hours after i.v., i.g., and p.o. administration, respectively. Total body clearance and steady-state volume of distribution were 0.41 +/- 0.10 L/h/kg and 0.82 +/- 0.15 L/kg, respectively. Mean Tmax for i.g. administration (0.22 hours) was significantly shorter than Tmax for p.o. administration (0.67 hours). The AUC after i.v. and p.o. administration was 64.7 +/- 16.6 mg x h/L and 60.5 +/- 17.0 mg x h/L, respectively, whereas AUC for the i.g. route was significantly less at 42.5 +/- 9.41 mg x h/L. Zidovudine was well absorbed after i.g. and p.o. administration with bioavailability values of 70 +/- 24% and 95 +/- 23%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Cats had slower clearance of zidovudine, compared with other species. Plasma concentrations of zidovudine were maintained above the minimum effective concentration for inhibiting FIV replication by 50% (0.07 microM [0.019 microg/mL] for wild-type FIV clinical isolate) for at least 12 hours after i.v., i.g., or p.o. administration.     

Pharmacokinetics of ibafloxacin in healthy cats

The pharmacokinetics of ibafloxacin following single and repeated administration of an oral gel formulation and the effect of food intake were investigated in cats. Ibafloxacin is a chiral fluoroquinolone available for clinical use as a racemic mixture of the R- and S-enantiomers. Plasma concentrations of ibafloxacin and its metabolites were determined using microbiological, LC-MS-MS and enantioselective capillary zone electrophoresis assays. Ibafloxacin was absorbed rapidly [time of maximum concentration (tmax) 2-3 h], reaching a mean maximum concentration (Cmax) of approximately 2.1 and 1.6 microg/mL for R- and S-ibafloxacin, respectively, following a single oral administration of the racemate at 15 mg/kg. Once absorbed, ibafloxacin was metabolized to 7-hydroxy-ibafloxacin and mainly to 8-hydroxy-ibafloxacin. Following repeated oral administration, significant increases in Cmax and AUC of ibafloxacin and its less active metabolites (racemic or enantiomers) were observed between the first and the tenth day of treatment. This twofold exposure increase in concentrations of ibafloxacin and its metabolites may contribute additionally to the efficacy of this drug in the treatment of feline bacterial infections. Single and repeated doses of ibafloxacin were well tolerated by cats. Food promoted the absorption of ibafloxacin, doubling Cmax and increasing AUC and slightly delaying tmax. High concentrations of the metabolites, mainly 8-hydroxy- and 7-hydroxy-ibafloxacin were excreted in urine, either unchanged or as glucurono-conjugates.     

Pharmacokinetics of midazolam in sevoflurane-anesthetized cats

ObjectiveTo estimate the pharmacokinetics of midazolam and 1-hydroxymidazolam after midazolam administration as an intravenous bolus in sevoflurane-anesthetized cats.Study designProspective pharmacokinetic study.AnimalsA group of six healthy adult, female domestic cats.MethodsAnesthesia was induced and maintained with sevoflurane. After 30 minutes of anesthetic equilibration, cats were administered midazolam (0.3 mg kg^–1) over 15 seconds. Venous blood was collected at 0, 1, 2, 4, 8, 15, 30, 45, 90, 180 and 360 minutes after administration. Plasma concentrations for midazolam and 1-hydroxymidazolam were measured using high-pressure liquid chromatography. The heart rate (HR), respiratory rate (f_R), rectal temperature, noninvasive mean arterial pressure (MAP) and end-tidal carbon dioxide (Pe′CO₂) were recorded at 5 minute intervals. Population compartment models were fitted to the time–plasma midazolam and 1-hydroxymidazolam concentrations using nonlinear mixed effect modeling.ResultsThe pharmacokinetic model was fitted to the data from five cats, as 1-hydroxymidazolam was not detected in one cat. A five-compartment model best fitted the data. Typical values (% interindividual variability where estimated) for the volumes of distribution for midazolam (three compartments) and hydroxymidazolam (two compartments) were 117 (14), 286 (10), 705 (14), 53 (36) and 334 mL kg^–1, respectively. Midazolam clearance to 1-hydroxymidazolam, midazolam fast and slow intercompartmental clearances, 1-hydroxymidazolam clearance and 1-hydroxymidazolam intercompartment clearance were 18.3, 63.5 (15), 22.1 (8), 1.7 (67) and 3.8 mL minute^–1 kg^–1, respectively. No significant changes in HR, MAP, f_R or Pe′CO₂ were observed following midazolam administration.Conclusion and clinical relevanceIn sevoflurane-anesthetized cats, a five-compartment model best fitted the midazolam pharamacokinetic profile. There was a high interindividual variability in the plasma 1-hydroxymidazolam concentrations, and this metabolite had a low clearance and persisted in the plasma for longer than the parent drug. Midazolam administration did not result in clinically significant changes in physiologic variables.     

Pharmacokinetics of cetirizine in healthy cats

OBJECTIVE: To develop a high-performance liquid chromatography (HPLC) assay for cetirizine in feline plasma and determine the pharmacokinetics of cetirizine in healthy cats after oral administration of a single dose (5 mg) of cetirizine dihydrochloride. ANIMALS: 9 healthy cats. PROCEDURES: Heparinized blood samples were collected prior to and 0.5, 1, 2, 4, 6, 8, 10, and 24 hours after oral administration of 5 mg of cetirizine dihydrochloride to each cat (dosage range, 0.6 to 1.4 mg/kg). Plasma was harvested and analyzed by reverse-phase HPLC. Plasma concentrations of cetirizine were analyzed with a compartmental pharmacokinetic model. Protein binding was measured by ultrafiltration with a microcentrifugation system. RESULTS: No adverse effects were detected after drug administration in the cats. Mean +/- SD terminal half-life was 10.06 +/- 4.05 hours, and mean peak plasma concentration was 3.30 +/- 1.55 microg/mL. Mean volume of distribution and clearance (per fraction absorbed) were 0.24 +/- 0.09 L/kg and 0.30 +/- 0.09 mL/kg/min, respectively. Mean plasma concentrations were approximately 2.0 microg/mL or higher for 10 hours and were maintained at > 0.72 microg/mL for 24 hours. Protein binding was approximately 88%. CONCLUSIONS AND CLINICAL RELEVANCE: A single dose of cetirizine dihydrochloride (approx 1 mg/kg, which corresponded to approximately 0.87 mg of cetirizine base/kg) was administered orally to cats. It was tolerated well and maintained plasma concentrations higher than those considered effective in humans for 24 hours after dosing. The half-life of cetirizine in cats is compatible with once-daily dosing, and the extent of protein binding is high.     

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)