title: Trans-pinnal movement of methimazole: an in vitro study showing that methimazole can cross from the inner to outer pinna of cats.
abstract: OBJECTIVE
  The aim of the study was to determine if methimazole applied in a transdermal formulation to the internal pinna will cross to the external pinna in an in vitro Franz cell model.
  
  
  METHODS
  The ears from six cats were harvested soon after death. Whole ears were mounted onto Franz-type diffusion cells with the stratum corneum of the inner pinnae uppermost. A commercial transdermal preparation containing methimazole (0.1 ml/10 mg) was applied to the inner pinnae. At 1, 2, 4, 6, 8, 12, 18, 24 and 30 h, a 200 µl sample of reservoir solution was removed to determine the methimazole concentration by high-performance liquid chromatography. The ears were then dissected, separating the internal pinna from the cartilage and the external pinna, before the methimazole concentration was measured at each site. The thickness of the different regions of the ear was measured on paraffin histology sections.
  
  
  RESULTS
  Mean ± SD methimazole concentrations at 30 h for the right and left ear, respectively, were: inner ear, 1.25 ± 0.53 mg/g, 0.39 ± 0.26 mg/g; cartilage, 1.36 ± 0.47 mg/g, 0.33 ± 0.20 mg/g; and outer ear, 1.0 ± 0.32 mg/g, 0.33 ± 0.14 mg/g. There was a difference between the left and right ears (P <0.001). Minimal methimazole concentrations were detected in the receptor fluid. The mean methimazole concentration absorbed by the skin after application of 10 mg was, for the right ear, 3.65 ± 1.27 mg/g and, for the left, 1.08 ± 0.27 mg/g. There was no correlation between methimazole concentrations and thickness of each region of the ear.
  
  
  CONCLUSIONS
  Methimazole in a lipophilic vehicle applied to the inner pinna will penetrate to the outer pinna of cats in an in vitro model, which may have safety implications for humans associated with cats treated with transdermal methimazole. Substantial inter-individual variation was found. Further research is required in the area of transdermal penetration of drugs in cats.
authors.affiliation: Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand k.hill@massey.ac.nz.
authors.forename: Kate E
authors.initials: KE
authors.lastname: Hill
authors.affiliation: Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Chambers
authors.affiliation: Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: Boyd R
authors.initials: BR
authors.lastname: Jones
authors.affiliation: Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: Charlotte F
authors.initials: CF
authors.lastname: Bolwell
authors.affiliation: Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: Dani
authors.initials: D
authors.lastname: Aberdein
authors.affiliation: The University of Queensland, School of Veterinary Science, The University of Queensland, Gatton, Australia.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Mills
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D013956:Antithyroid Agents / Q000493:pharmacokinetics*; D001696:Biomechanical Phenomena; D002371:Cat Diseases / Q000188:drug therapy; D002415:Cats; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D054644:Ear Auricle / Q000187:drug effects*; D004431:Ear, External / Q000187:drug effects*; D008713:Methimazole / Q000493:pharmacokinetics*
chemical_list: D013956:Antithyroid Agents; D008713:Methimazole