Comparison of pharmacodynamic variables following oral versus transdermal administration of atenolol to healthy cats

MacGregor, John; Rozanski, Elizabeth A.; Boothe, Dawn M.; Belmonte, Albert A.; Freeman, Lisa M.

doi:10.2460/ajvr.69.1.39

Cited by 25 publications

(16 citation statements)

References 30 publications

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“…[3][4][5][6][7][8] The transdermal application of drugs has become popular in feline medicine, as cats can be difficult to consistently medicate PO. [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] The vehicle carrier affects the absorption of drugs across the skin by having a primary role in determining the partition coefficient for the drug and can also alter the properties of the skin. 28 The correct vehicle is required for each drug for maximum transdermal penetration.…”

Section: Discussionmentioning

confidence: 99%

“…Because of this, many compounding pharmacies have started formulating drugs into gels, which are applied to the inner side of the cat's ear and are thought to be absorbed through the skin for systemic action. [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] Not all drugs are suitable for transdermal penetration and only a few drugs have been studied in cats to determine whether they reach therapeutic concentrations after absorption by this route. [21][22][23]26,27,30,31 There are several factors that affect the transdermal delivery of drugs.…”

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confidence: 99%

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The Efficacy and Safety of a Novel Lipophilic Formulation of Methimazole for the Once Daily Transdermal Treatment of Cats with Hyperthyroidism

Hill

Gieseg

Kingsbury

et al. 2011

Veterinary Internal Medicne

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Background: Previous studies on transdermal methimazole have used pluronic lecithin organogel as the vehicle. This might not be the most suitable vehicle for a lipophilic drug, such as methimazole.Hypothesis/Objectives: Once daily transdermal administration of a novel lipophilic formulation of methimazole is as safe and effective as oral carbimazole in treating hyperthyroidism in cats.Animals: Forty-five client-owned cats diagnosed with hyperthyroidism. Methods: Prospective study. Cats with newly diagnosed, untreated hyperthyroidism were treated with carbimazole (5 mg PO, q12h) or methimazole (10 mg) applied to the inner pinnae q24h. Cats were examined after 0, 1, 4, 8, and 12 weeks of treatment. Clinical signs, body weight, systolic blood pressure, hematologic, serum biochemical and urine parameters, total serum thyroxine concentrations (TT4), and serum methimazole concentrations were recorded.Results: No significant differences between groups were detected at day 0. Both formulations were effective in treating hyperthyroidism. No significant differences were detected in thyroxine concentrations, body weight, blood pressure, heart rate, alkaline phosphatase, alanine aminotransferase, creatinine, urea, and urine specific gravity (USG) between groups. The serum methimazole concentrations correlated poorly with TT4-concentrations in both groups.Conclusions and Clinical Importance: In this 12-week trial, once daily application of a novel formulation of transdermal methimazole applied to the pinnae was as effective and safe as twice daily oral carbimazole in the treatment of cats with hyperthyroidism. This novel formulation and transdermal application could have practical advantages to some pet owners.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Efficacy and Safety of a Novel Lipophilic Formulation of Methimazole for the Once Daily Transdermal Treatment of Cats with Hyperthyroidism

Hill

Gieseg

Kingsbury

et al. 2011

Veterinary Internal Medicne

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“…MacGregor et al 35 and Quinones et al 36 evaluated the pharmacokinetic and pharmacodynamic effects of orally administered atenolol in healthy cats. These studies revealed that atenolol induces a time-dependent effect on HR that lasts for at least 12 h with peak serum concentrations and HR-lowering effects observed one to 2 h after administration.…”

Section: Discussionmentioning

confidence: 99%

“…These studies revealed that atenolol induces a time-dependent effect on HR that lasts for at least 12 h with peak serum concentrations and HR-lowering effects observed one to 2 h after administration. 35,36 This led to the conclusion that atenolol should be administered twice daily for effective HR control in cats. Our study revealed a similar effect of ivabradine on mean HR in healthy cats with a slightly different peak effect, but a comparable duration of action.…”

Section: Discussionmentioning

confidence: 99%

Pharmacodynamic effects of ivabradine, a negative chronotropic agent, in healthy cats

Cober

Schober

Buffington

et al. 2011

Journal of Veterinary Cardiology

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Objective To determine the pharmacodynamic effects of oral ivabradine in cats. Animals Eight healthy, adult domestic short hair cats. Methods Each cat underwent four study periods of 24 h, receiving either one dose of placebo or ivabradine (0.1 mg/kg, 0.3 mg/kg, and 0.5 mg/kg) in a single-blind randomized crossover study. Clinical tolerance was assessed hourly for the first 8 h, at 12 h, and at the end of the 24-h study period. Heart rate and blood pressure were monitored continuously for 18–24 h via radiotelemetry after each treatment. Response to stress (acoustic startle) was studied before (t = 0) and after treatment (t = 4 h). Statistical comparisons were made using a linear mixed models and 1-way and 2-way repeated measures ANOVA. Results Heart rate (min−1) decreased significantly (P < 0.05) in a dose-dependent manner with peak negative chronotropic effects observed 3 h after ivabradine (mean ±SD; placebo, 144 ± 20; ivabradine 0.1 mg/kg, 133 ±22; ivabradine 0.3 mg/kg, 112 ±20; and ivabradine 0.5 mg/kg, 104 ±11). Heart rate (min−1) was still reduced (P < 0.05) 12 h after ivabradine (0.3 mg/kg; 128 ±18 and 0.5 mg/kg; 124 ±16) compared to placebo (141 ±21). The tachycardic response to acoustic startle was significantly (P < 0.01) blunted at all 3 doses of ivabradine. Myocardial oxygen consumption estimated by the rate-pressure product was significantly reduced (P < 0.05) for all doses of ivabradine. No effect of ivabradine on systolic, diastolic, and mean blood pressure was identified and no clinically discernable side effects were observed. Conclusion These findings indicate that a single oral dose of ivabradine predictably lowers heart rate, blunts the chronotropic response to stress, and is clinically well tolerated in healthy cats. This makes ivabradine potentially interesting in the treatment of feline heart disease where ischemia is of pathophysiologic importance.

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“…In addition, the heart rate-lowering actions of ivabradine were similar to those of atenolol, a drug commonly used in cats with hypertrophic cardiomyopathy. MacGregor et al (2008) and Quiñ ones et al (1996) evaluated the pharmacokinetic and pharmacodynamic effects of orally administered atenolol on heart rate in healthy cats. Our results revealed a similar effect of ivabradine on mean heart rate in healthy cats with a slightly different peak effect, but a comparable duration of action thereby encouraging the oral use of ivabradine in the clinical setting.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of oral ivabradine in healthy cats

Riesen

Carnes

et al. 2010

Vet Pharm & Therapeutics

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A liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method for the measurement of the novel heart rate-lowering drug ivabradine and its major metabolite, S-18982, was cross-validated in the plasma of eight healthy cats. Plasma concentrations were then determined after single and repeated oral administration of ivabradine. Individual plasma concentrations versus time from each cat were used in compartmental analysis using the commercially available software WinNonlin. Both ivabradine and S-18982 reached their maximum concentrations of 103.33 and 3.86 ng/mL within 1 h. Following repeated administration, areas under the plasma concentration-time curves for ivabradine and S-18982 did not significantly increase. Two-compartmental and one-compartmental models with first-order input and elimination provided the best fit to the data for ivabradine and S-18982, respectively. Both models were combined to produce a single 4-compartment model characterizing ivabradine and S-18982 pharmacokinetics. The results of this study indicate that repeated oral doses of ivabradine produced plasma drug concentrations suitable for 12-h dosing intervals in healthy cats. Furthermore, the analytical assay and combined ivabradine/S-18982 model provide tools for further evaluation of ivabradine pharmacokinetics and pharmacodynamics in future studies in cats.

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Comparison of pharmacodynamic variables following oral versus transdermal administration of atenolol to healthy cats

Cited by 25 publications

References 30 publications

The Efficacy and Safety of a Novel Lipophilic Formulation of Methimazole for the Once Daily Transdermal Treatment of Cats with Hyperthyroidism

The Efficacy and Safety of a Novel Lipophilic Formulation of Methimazole for the Once Daily Transdermal Treatment of Cats with Hyperthyroidism

Pharmacodynamic effects of ivabradine, a negative chronotropic agent, in healthy cats

Pharmacokinetics of oral ivabradine in healthy cats

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