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

Abstract

To investigate associations between short-term treatment with a previously described compounded transdermal formulation of atenolol and heart rate in cats. 11 healthy adult cats. 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). 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. 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.