Drug exposure and clinical effect of transdermal mirtazapine in healthy young cats: a pilot study

Abstract

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.

Single and multiple dose pharmacokinetics of a novel mirtazapine transdermal ointment in cats

“…For single dose transdermal application of mirtazapine ointment in healthy young cats, serum PK parameters seen in a previously published study were again generally comparable with that reported in Study 1 (Table ) (Benson et al., ). However, the previously reported lipoderm gel formulation appeared to produce a somewhat flatter drug concentration curve and thus a lower mean C max compared to the novel ointment formulation, even at a higher mg/kg dose.…”

“…The PK of mirtazapine in cats has been previously described for an oral capsule formulation in healthy young cats, healthy geriatric cats, and cats with chronic kidney disease, as well as for transdermal lipoderm gel in healthy young cats (Tables and ) (Quimby, Gustafson, & Lunn, ; Quimby, Gustafson, Samber et al., ; Benson et al., ). Meaningful comparisons between studies with different formulations and populations of cats from various sites are limited, however, the following discussion relates to general concepts.…”

The pharmacokinetics of gabapentin in cats

“…Our data also suggest that gabapentin (as prepared in this study) has minimal transdermal absorption, and is not an appropriate route of administration. The transdermal vehicle was chosen because of its drug delivery properties, and its common use in practice . These data are relevant given the increasing interest in compounding of transdermal preparations for cats …”

A double‐blind, placebo‐controlled, randomized study to evaluate the weight gain drug, mirtazapine transdermal ointment, in cats with unintended weight loss

“…It is less haired, highly vascular, and thinner than other anatomical locations which may improve transdermal absorption (Hill et al., ) and is a common site of application for other topical ointments in the cat. (Bennett, Papich, Hoenig, Fettman, & Lappin, ; Benson et al., ; Ciribassi et al., ; Hill et al., ; Mealey et al., ; Miller, Schick, Boothe, & Lewis, ).…”