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1.
The use of transdermal gel medications in cats has become popular in veterinary medicine due to the ease of administration compared to oral medication. The research to support systemic absorption of drugs after transdermal gel administration and the preferred skin region to apply these drugs in cats is limited. The aim of this study was to characterize the effect of different skin regions on the percutaneous absorption pharmacokinetics of a commercially available transdermal methimazole after a finite dose was applied to feline skin in vitro. A commercial formulation of methimazole (10 mg) was applied to four skin regions (the inner stratum corneum of the ear, groin, neck, and thorax regions) from six cats. The receptor medium was sampled up to 36 h postapplication, and methimazole concentrations were measured using high‐performance liquid chromatography. Methimazole was absorbed more completely across the pinnal skin, compared to the groin, neck, and thorax (P < 0.001), which justifies application to the pinna to maximize efficacy and also to minimize the effects of grooming.  相似文献   

2.
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.  相似文献   

3.

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.  相似文献   

4.
The objective of this study was to determine whether transdermal methimazole was as safe and effective as oral methimazole for the control of hyperthyroidism in cats. Forty-seven cats with newly diagnosed hyperthyroidism were randomized to receive either transdermal methimazole in pluronic lecithin organogel (PLO; applied to the inner pinna), or oral methimazole (2.5 mg q12h for either route). Cats were evaluated at weeks 0, 2, and 4 with a physical exam, body weight determination, CBC, biochemical panel, urinalysis, measurement of total levothyroxine (T4) concentration, indirect Doppler blood pressure determinaiton, and completion of an owner questionnaire. Data between the 2 groups and over time were compared by nonparametric methods. Forty-four cats followed the protocol (17 oral and 27 transdermal). Significantly more cats treated with oral methimazole had serum T4 concentrations within the reference range after 2 weeks (14 of 16 cats) compared to those treated by the transdermal route (14 of 25; P = .027). This difference was no longer significant by 4 weeks of treatment (9 of 11 for oral versus 14 of 21 for transdermal), possibly because of inadequate numbers evaluated by 4 weeks. Cats treated with oral methimazole had a higher incidence of gastrointestinal (GI) adverse effects (4 of 17 cats) compared to the cats treated with transdermal methimazole (1 of 27; P = .04), but no differences were found between groups in the incidence of neutropenia, hepatotoxicity, or facial excoriations. Although the overall efficacy of transdermal methimazole is not as high as that of oral methimazole at 2 weeks of treatment, it is associated with fewer GI adverse effects compared to the oral route.  相似文献   

5.
A prospective study was performed to determine the relative availability of buspirone and amitriptyline after oral and transdermal routes of administration in 6 adult cats. For topical administration, drugs were compounded in a transdermal organogel containing pluronic and lecithin (PLO). Using a crossover design, each cat received a single dose of amitriptyline (5 mg) and buspirone (2.5 mg) by the transdermal and oral route of administration with at least a 2-week washout interval between drug treatments. Blood samples were obtained at 0, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after drug administration for determination of plasma drug concentrations. Plasma concentrations of immunoreactive amitriptyline and buspirone were determined using commercial enzyme-linked immunosorbent assay (ELISA) tests. Systemic absorption of amitriptyline and buspirone administered by the transdermal route was poor compared with the oral route of administration. Until supporting pharmacokinetic data are available, veterinarians and cat owners should not rely on the transdermal route of administration for treating cats with amitriptyline or buspirone.  相似文献   

6.
Transdermal methimazole treatment in cats with hyperthyroidism   总被引：1，自引：0，他引：1  
The objectives of this study were to assess serum thyroxine concentrations and clinical response in hyperthyroid cats to treatment with transdermal methimazole, and to determine if further investigation is indicated.Clinical and laboratory data from 13 cats with hyperthyroidism were retrospectively evaluated. Methimazole (Tapazole, Eli Lilly) was formulated in a pleuronic lecithin organogel (PLO)-based vehicle and was applied to the inner pinna of the ear at a dosage ranging from 2.5mg/cat q 24h to 10.0mg/cat q 12h. During the treatment period, cats were re-evaluated at a mean of 4.3 weeks (recheck-1), and again at a mean of 5.4 months (recheck-2).Clinical improvement was observed, and significant decreases in thyroxine concentrations were measured at recheck-1 (mean: 39.57nmol/L, SEM: 14.4, SD: 41.2) and recheck-2 (mean: 36.71nmol/L, SEM: 13.9, SD: 45.56) compared to pretreatment concentrations (mean: 97.5nmol/L, SEM: 11.42, SD: 39.5). No adverse effects were reported.  相似文献   

7.
OBJECTIVE: To determine bioavailability, pharmacokinetics, and safety for transdermal (TD) and oral administration of fluoxetine hydrochloride to healthy cats. ANIMALS: 12 healthy mixed-breed sexually intact 1- to 4-year-old purpose-bred cats. PROCEDURE: A single-dose pharmacokinetic study involving 3 groups of 4 cats each was conducted in parallel. Fluoxetine in a formulation of pluronic lecithin organogel (PLO gel) was applied to the hairless portion of the pinnae of cats at 2 dosages (5 or 10 mg/kg), or it was administered orally in capsules at a dosage of 1 mg/kg. Plasma samples were obtained and submitted for liquid chromatography-mass spectrometry-mass spectrometry analysis of fluoxetine and its active metabolite, norfluoxetine. RESULTS: Peak fluoxetine concentration (Cmax) was lower and time to Cmax longer for TD administration versus oral administration. Relative bioavailability of each dose administered via the TD route was 10% of the value for oral administration of the drug. Mean plasma elimination half-life after oral administration was 47 and 55 hours for fluoxetine and norfluoxetine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: This study provides evidence that fluoxetine in a 15% (wt:vol) PLO gel formulation can be absorbed through the skin of cats into the systemic circulation. However, the relative bioavailability for TD administration is approximately only 10% of that for the oral route of administration.  相似文献   

8.
Flunixin is a nonsteroidal anti-inflammatory drug (NSAID) that has anti-inflammatory, anti-pyretic, and analgesic effects. Recently, a novel transdermal formulation was developed (Finadyne® Transdermal, MSD Animal Health) and is now the first NSAID registered to be administered as a pour-on product in cattle. According to the manufacturer's instructions, the pour-on product should be applied only to dry skin and exposure to rain should be avoided for at least 6 hr after application. The objective of the study was to evaluate the effect of simulated exposure to light or heavy rain on flunixin absorption and bioavailability within the first 4 hr after administration. Therefore, an isocratic HPLC method was developed to quantify flunixin concentrations in bovine serum by UV detection. Light rain decreased flunixin absorption only when rain started immediately after flunixin administration, while light rain starting more than 30 min after administration of flunixin had no effect on absorption. Absorption and bioavailability of flunixin was impacted under simulated heavy rain conditions, when exposure to rain occurred within one hour after the application of the pour-on formulation, but not later.  相似文献   

9.
Topical application of ectoparasiticides for flea and tick control is a major focus for product development in animal health. The objective of this work was to develop a quantitative structure permeability relationship (QSPeR) model sensitive to formulation effects for predicting absorption and skin deposition of five topically applied drugs administered in six vehicle combinations to porcine and canine skin in vitro. Saturated solutions (20 μL) of 14C‐labeled demiditraz, fipronil, permethrin, imidacloprid, or sisapronil were administered in single or binary (50:50 v/v) combinations of water, ethanol, and transcutol (6 formulations, n = 4–5 replicates per treatment) nonoccluded to 0.64 cm2 disks of dermatomed pig or dog skin mounted in flow‐through diffusion cells. Perfusate flux over 24 h and skin deposition at termination were determined. Permeability (logKp), absorption, and penetration endpoints were modeled using a four‐term Abrahams and Martin (hydrogen‐bond donor acidity and basicity, dipolarity/polarizability, and excess molar refractivity) linear free energy QSPeR equation with a mixture factor added to compensate for formulation ingredient interactions. Goodness of fit was judged by r2, cross‐validation coefficient, coefficients (q2s), and Williams Plot to visualize the applicability domain. Formulation composition was the primary determinant of permeation. Compounds generally penetrated dog skin better than porcine skin. The vast majority of permeated penetrant was deposited within the dosed skin relative to transdermal flux, an attribute for ectoparasiticides. The best QSPeR logKp model for pig skin permeation (r2 = 0.86, q2s = 0.85) included log octanol/water partition coefficient as the mixture factor, while for dogs (r2 = 0.91, q2s = 0.90), it was log water solubility. These studies clearly showed that the permeation of topical ectoparasiticides could be well predicted using QSPeR models that account for both the physical–chemical properties of the penetrant and formulation components.  相似文献   

10.
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.  相似文献   

11.
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.  相似文献   

12.
Thirteen cats, newly diagnosed with hyperthyroidism, were treated with a transdermal formulation of methimazole at a dose of 5 mg (0.1 mL) (concentration of 50 mg/mL) applied to the internal ear pinna every 12 h for 28 d. Baseline hematologic and biochemical values, along with serum thyroxine (T4) levels, were obtained on presentation (day 0). Cats were evaluated at 14 d (D14) and 28 d (D28) following transdermal therapy. At each visit, a physical examination, a complete blood cell count, a serum biochemical analysis, and a serum T4 evaluation were performed. Ten cats completed the study. Clinical improvement, as well as a significant decrease in T4, was noted in all cats. Serum T4 measured at D14 and D28 were significantly lower at 27.44 nmol/L, s = 37.51 and 14.63 nmol/L, s = 10.65, respectively (P < 0.0001), as compared with values at D0 (97.31 nmol/L, s = 37.55). Only 1 cat showed a cutaneous adverse reaction along with a marked thrombocytopenia. The results of this prospective clinical study suggest that transdermal methimazole is an effective and safe alternative to conventional oral formulations.  相似文献   

13.
Data allowing rational use of analgesics in cats are limited. Pharmacokinetics and pharmacodynamics of fentanyl were studied in cats. Plasma fentanyl concentrations were measured using radioimmunoassay in a crossover study in six cats after 10 microg/kg (i.v.) or by application of fentanyl in pluronic lecithin organogel (PLO) to the inner ear pinna. On a separate occasion thermal thresholds were measured after i.v. fentanyl (10 microg/kg) or saline. Plasma fentanyl concentrations reached 4.7-8.31 ng/mL 2 min after i.v. administration and were undetectable after 95 min. Fentanyl was not detected in plasma at any time after PLO use. Thermal thresholds did not change following saline administration but were increased above baseline from 5 to 110 min after i.v. fentanyl. In this model a plasma concentration of >1.07 ng/mL was required to provide analgesia. Plasma concentrations were measured in additional cats after intranasal or oral dosing (2 microg/kg) and after 30 microg/kg in PLO gel. After oral and nasal dosing, Cmax values were 0.96 and 1.48 ng/mL at 5 and 2 min, respectively. Plasma fentanyl was not detected after application of the higher dose of fentanyl in PLO.  相似文献   

14.
Suberoylanilide hydroxamic acid (SAHA), or vorinostat, is a histone deacetylase inhibitor approved for use as chemotherapy for lymphoma in humans. The goal of this study was to establish pharmacological parameters of SAHA in cats. Our interest in treating cats with SAHA is twofold: as an anticancer chemotherapeutic and as antilatency therapy for feline retroviral infections. Relying solely on data from studies in other animals would be inappropriate as SAHA is partially metabolized by glucuronidation, which is absent in feline metabolism. SAHA was administered to cats intravenously (2 mg/kg) or orally (250 mg/m2, ~17 mg/kg) in a cross‐over study design. Clinically, SAHA was well tolerated at these dosages as no abnormalities were noted following administration. The pharmacokinetics of SAHA in cats was found to be similar to that of dogs, but the overall serum drug exposure was much less than that of humans at an equivalent dose. The pharmacodynamic effect of an increase in acetylated histone proteins in blood was detected after both routes of administration. An increased oral dose of 60 mg SAHA/kg administered to one animal resulted in a surprisingly modest increase in peak drug concentration, suggesting possible saturation of absorption kinetics. This study provides a foundation for future studies of the clinical efficacy of SAHA in treating feline disease.  相似文献   

15.
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 (tmax 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.  相似文献   

16.
Hyperthyroidism is the most common feline endocrinopathy; thyroid computed tomography (CT) may improve disease detection and methimazole dose selection. Objectives of this experimental pre‐post with historical case‐control study were to perform thyroid CT imaging in awake or mildly sedated hyperthyroid cats, compare thyroid gland CT appearance in euthyroid and hyperthyroid cats pre‐ and postmethimazole treatment, and determine whether thyroid size or attenuation correlate with methimazole dose needed for euthyroidism. Premethimazole treatment, eight hyperthyroid cats received CT scans from the head to heart, which were compared to CT of seven euthyroid cats. Total thyroxine levels were monitored every 3–4 weeks. Postmethimazole CT was performed 30 days after achieving euthyroid status. Computed tomography parameters recorded included thyroid length, width, height, attenuation, and heterogeneity. Median time between CT was 70 days (53–213 days). Mild sedation was needed in five hyperthyroid cats premethimazole, and none postmethimazole. Thyroid volume was significantly larger in hyperthyroid cats compared to euthyroid cats (785.0 mm3 vs. 154.9 mm3; P = 0.002) and remained unchanged by methimazole treatment (?4.5 mm3; P = 0.50). Thyroid attenuation and heterogeneity decreased with methimazole treatment (96.1 HU vs. 85.9 HU; P = 0.02. 12.4 HU vs. 8.1 HU; P = 0.009). Methimazole dose ranged from 2.5 to 10 mg daily with a positive correlation between pretreatment thyroid gland volume and dose needed to achieve euthyroidism (P = 0.03). Euthyroid and hyperthyroid cats are easily imaged awake or mildly sedated with CT. Methimazole in hyperthyroid cats significantly lowers thyroid attenuation and heterogeneity, but not size.  相似文献   

17.
Repeated administration of meloxicam can cause kidney damage in cats by mechanisms that remain unclear. Metabolomics and lipidomics are powerful, noninvasive approaches used to investigate tissue response to drug exposure. Thus, the objective of this study was to assess the effects of meloxicam on the feline kidney using untargeted metabolomics and lipidomics approaches. Female young‐adult purpose‐breed cats were allocated into the control (n = 4) and meloxicam (n = 4) groups. Cats in the control and meloxicam groups were treated daily with saline and meloxicam at 0.3 mg/kg subcutaneously for 17 days, respectively. Renal cortices and medullas were collected at the end of the treatment period. Random forest and metabolic pathway analyses were used to identify metabolites that discriminate meloxicam‐treated from saline‐treated cats and to identify disturbed metabolic pathways in renal tissue. Our results revealed that the repeated administration of meloxicam to cats altered the kidney metabolome and lipidome and suggest that at least 40 metabolic pathways were altered in the renal cortex and medulla. These metabolic pathways included lipid, amino acid, carbohydrate, nucleotide and energy metabolisms, and metabolism of cofactors and vitamins. This is the first study using a pharmacometabonomics approach for studying the molecular effects of meloxicam on feline kidneys.  相似文献   

18.
Mirtazapine is classified as a weight gain drug in cats, and the purpose of this study was to evaluate its efficacy in cats experiencing unintended weight loss. This was a multi‐center, double‐blind, placebo‐controlled, randomized clinical study in client‐owned cats ≥1 year of age, weighing ≥2 kg, with a documented loss (≥5%) in body weight. Cats were treated once daily with either 2 mg/cat mirtazapine transdermal ointment (n = 83) or placebo (n = 94) (Per Protocol population) applied to the inner surface of the pinna for 14 ± 3 days. Physical examination, body weight, complete blood count, serum chemistry, and urinalysis were performed prior to treatment and on Day 14. Changes in body weight between the mirtazapine and placebo groups were evaluated from Day 1 to Day 14 and compared using a two‐sample t test. The mean percent change in body weight was +3.9% (standard deviation ±5.4%) in the mirtazapine group and +0.4% (±3.3%) in the placebo group (p < 0.0001). The most common adverse event was mild erythema at the application site in 17.4% of placebo and 10.4% of mirtazapine‐treated cats. Application of mirtazapine transdermal ointment was well tolerated both topically and systemically and resulted in significant weight gain in cats experiencing unintended weight loss associated with various underlying diseases.  相似文献   

19.
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20.
Single and multiple dose pharmacokinetics (PK) of mirtazapine transdermal ointment applied to the inner ear pinna of cats were assessed. Study 1 was a randomized, cross‐over single dose study (n = 8). Cats were treated once with 0.5 mg/kg of mirtazapine transdermal ointment applied topically to the inner ear pinna (treatment) or administered orally (control) and then crossed over after washout. Plasma was collected predose and at specified intervals over 96 hr following dosing. Study 2 was a multiple dose study (n = 8). Cats were treated daily for 14 days with 0.5 mg/kg of mirtazapine transdermal ointment applied topically to the inner pinna. Plasma was collected on Day 13 predose and at specified intervals over 96 hr following the final dose. In Study 1, single transdermal administration of mirtazapine resulted in mean Tmax = 15.9 hr, Cmax = 21.5 ng/mL, AUC0‐24 = 100 ng*hr/mL, AUC0‐∞ = 260 ng*hr/mL and calculated half‐life = 26.8 hr. Single oral administration of mirtazapine resulted in mean Tmax = 1.1 hr, Cmax = 83.1 ng/mL, AUC0‐24 = 377 ng*hr/mL, AUC0‐∞ = 434 ng*hr/mL and calculated half‐life = 10.1 hr. Mean relative bioavailability (F) of transdermal to oral dosing was 64.9%. In Study 2, daily application of mirtazapine for 14 days resulted in mean Tmax = 2.1 hr, Cmax = 39.6 ng/mL, AUC0‐24 = 400 ng*hr/mL, AUC0‐∞ = 647 ng*hr/mL and calculated half‐life = 20.7 hr. Single and repeat topical doses of a novel mirtazapine transdermal ointment achieve measurable plasma concentrations in cats.  相似文献   

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