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Single and multiple dose pharmacokinetics of a novel mirtazapine transdermal ointment in cats
Author(s) -
Buhles William,
Quimby Jessica M.,
Labelle Daizie,
Williams Valentine S.
Publication year - 2018
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12691
Subject(s) - mirtazapine , cmax , pharmacokinetics , transdermal , dosing , pharmacology , medicine , bioavailability , pinna , oral administration , pharmacodynamics , anesthesia , surgery , hippocampus , antidepressant
Single and multiple dose pharmacokinetics ( PK ) of mirtazapine transdermal ointment applied to the inner ear pinna of cats were assessed. Study 1 was a randomized, cross‐over single dose study ( n = 8). Cats were treated once with 0.5 mg/kg of mirtazapine transdermal ointment applied topically to the inner ear pinna (treatment) or administered orally (control) and then crossed over after washout. Plasma was collected predose and at specified intervals over 96 hr following dosing. Study 2 was a multiple dose study ( n = 8). Cats were treated daily for 14 days with 0.5 mg/kg of mirtazapine transdermal ointment applied topically to the inner pinna. Plasma was collected on Day 13 predose and at specified intervals over 96 hr following the final dose. In Study 1, single transdermal administration of mirtazapine resulted in mean T max = 15.9 hr, C max = 21.5 ng/ mL , AUC 0‐24 = 100 ng*hr/ mL , AUC 0‐∞ = 260 ng*hr/ mL and calculated half‐life = 26.8 hr. Single oral administration of mirtazapine resulted in mean T max = 1.1 hr, C max = 83.1 ng/ mL , AUC 0‐24 = 377 ng*hr/ mL , AUC 0‐∞ = 434 ng*hr/ mL and calculated half‐life = 10.1 hr. Mean relative bioavailability ( F ) of transdermal to oral dosing was 64.9%. In Study 2, daily application of mirtazapine for 14 days resulted in mean T max = 2.1 hr, C max = 39.6 ng/ mL , AUC 0‐24 = 400 ng*hr/ mL , AUC 0‐∞ = 647 ng*hr/ mL and calculated half‐life = 20.7 hr. Single and repeat topical doses of a novel mirtazapine transdermal ointment achieve measurable plasma concentrations in cats.