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Investigation of the short-term effects of a transdermal formulation of atenolol in healthy cats

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  • 1 From the Department of Clinical Sciences, Carlson College of Veterinary Medicine (LeBlanc, Scollan), and College of Pharmacy (Mohamed, Christensen), Oregon State University, Corvallis, OR 97331.

Abstract

OBJECTIVE

To investigate associations between short-term treatment with a previously described compounded transdermal formulation of atenolol and heart rate in cats.

ANIMALS

11 healthy adult cats.

PROCEDURES

Cats received the atenolol gel formulation (gradually increased from 12.5 mg/cat, q 24 h to 25 mg/cat, q 12 h) by application to the pinnae at home over a 10-day period in a prospective, experimental study. On day 10, cats were hospitalized for measurement of serum atenolol concentrations 3, 6, and 12 hours after the morning treatment. Mean heart rate measured at the 3- and 6-hour time points was compared with a baseline value (measured at enrollment).

RESULTS

All cats completed the study; 4 were excluded from analyses after an apparent formulation error was detected in 1 batch. Two cats had minor adverse effects (localized erythema of the pinna). Five of 7 cats had serum atenolol concentrations ≥ 260 ng/mL (considered therapeutic) at ≥ 1 time point. Heart rate had a strong negative correlation (r =–0.87) with serum atenolol concentration. A 90-day drug stability investigation of 4 formulations (identical to the intended study treatment except for pH [range, 6.5 to 7.7]) revealed an apparent decrease in atenolol concentration at a pH of 7.7.

CONCLUSIONS AND CLINICAL RELEVANCE

Topical administration of the formulation as described resulted in targeted serum atenolol concentrations in most cats, with attendant HR reduction. Validation of these preliminary results in a larger sample and investigation of the treatment in cats with structural heart disease is needed. Verification of appropriate pH (target, 7.0) is likely essential for the compound's stability.

Abstract

OBJECTIVE

To investigate associations between short-term treatment with a previously described compounded transdermal formulation of atenolol and heart rate in cats.

ANIMALS

11 healthy adult cats.

PROCEDURES

Cats received the atenolol gel formulation (gradually increased from 12.5 mg/cat, q 24 h to 25 mg/cat, q 12 h) by application to the pinnae at home over a 10-day period in a prospective, experimental study. On day 10, cats were hospitalized for measurement of serum atenolol concentrations 3, 6, and 12 hours after the morning treatment. Mean heart rate measured at the 3- and 6-hour time points was compared with a baseline value (measured at enrollment).

RESULTS

All cats completed the study; 4 were excluded from analyses after an apparent formulation error was detected in 1 batch. Two cats had minor adverse effects (localized erythema of the pinna). Five of 7 cats had serum atenolol concentrations ≥ 260 ng/mL (considered therapeutic) at ≥ 1 time point. Heart rate had a strong negative correlation (r =–0.87) with serum atenolol concentration. A 90-day drug stability investigation of 4 formulations (identical to the intended study treatment except for pH [range, 6.5 to 7.7]) revealed an apparent decrease in atenolol concentration at a pH of 7.7.

CONCLUSIONS AND CLINICAL RELEVANCE

Topical administration of the formulation as described resulted in targeted serum atenolol concentrations in most cats, with attendant HR reduction. Validation of these preliminary results in a larger sample and investigation of the treatment in cats with structural heart disease is needed. Verification of appropriate pH (target, 7.0) is likely essential for the compound's stability.

Supplementary Materials

    • Supplementary Appendix S1 (PDF 101 KB)

Contributor Notes

Address correspondence to Dr. LeBlanc (nikbleu@gmail.com).