Objectives Measure drug exposure and clinic effects after administration of transdermal mirtazapine (TMZ) in healthy cats. Methods Phase I: Seven healthy research cats received A) 3.75 mg and 7.5 mg TMZ once aurally with 48 hour serum sampling (serum samples were obtained via jugular catheter at 0, 0.5, 1, 2, 5, 9, 12, 24, 36 and 48 h), B) 7.5 mg TMZ and placebo daily aurally for six days then 48 h serum sampling C) 1.88 mg mirtazapine orally once with serum sampling at 1, 4 and 8 h. Phase II: Twenty client-owned cats were enrolled in a randomized double-blind placebo-controlled three-way crossover clinical effect study. Treatments consisted of six days of aural 7.5 mg TMZ or placebo gel at home, and 1.88 mg mirtazapine orally once in clinic. Owners documented appetite, rate of food ingestion, begging, activity and vocalization daily at home. On day six, food consumed, activity and vocalization were documented in hospital and trough and peak serum mirtazapine levels obtained. Serum mirtazapine and gel concentrations were measured using liquid chromatography/tandem mass spectrometry. Results Phase I: Administration of TMZ achieved measureable serum mirtazapine concentrations. AUC0-48 of multidose 7.5 mg TMZ was significantly higher than single dose 1.88 mg OMZ (P = 0.02). Phase II: Client-owned cats administered TMZ had a significant increase in appetite (P = 0.003), rate of food ingestion (P = 0.002), activity (P = 0.002), begging (P = 0.002) and vocalization (P = 0.002) at home. In hospital there was a significant increase in food ingested with both TMZ and OMZ compared to placebo (P < 0.05). Gel concentrations ranged from 87%–119% of target dose. Conclusions and relevance 7.5 mg daily TMZ achieves measureable serum concentrations and significant appetite stimulation despite variance in compounded gel concentrations, but side effects denote a lower dose is indicated.

Objectives The objective of this study was to assess the absorption of transdermal ondansetron in healthy cats. Methods Five research cats with unremarkable complete blood count, biochemistry and urinalysis were used for both single- and multiple-dose application studies. For single-dose application, 4 mg ondansetron in 0.1 ml Lipoderm gel was applied once to the internal ear pinna. Blood samples were collected via jugular catheter over a 48 h period following administration (0, 15 mins, 30 mins, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h and 48 h). For multiple-dose application, 4 mg ondansetron in 0.1 ml Lipoderm gel was applied for five consecutive days before blood samples were obtained in the same manner. Serum was separated and frozen prior to analysis. Ondansetron was measured via liquid chromatography coupled to tandem mass spectrometry. Results Analysis revealed no clinically relevant drug levels in serum after either single- or multiple-dose administration of 4 mg transdermal ondansetron. Conclusions and relevance Transdermal application of 4 mg ondansetron does not result in clinically relevant serum concentrations of drug. Despite characteristics of the drug that imply suitability for transdermal application, this does not appear to be an acceptable method of drug delivery for this medication at this dose. This study highlights the importance of assessing the suitability of each medication for transdermal administration.