Bioavailability of transdermal methimazole in a pluronic lecithin organogel (PLO) in healthy cats

Abstract

The antithyroid drug methimazole is widely used for the medical management of feline hyperthyroidism. Recently, custom veterinary pharmacies have offered methimazole in a transdermal gel containing pluronic and lecithin (PLO), with anecdotal evidence of efficacy. The purpose of this study was to determine the bioavailability, relative to i.v. and oral routes of administration, of transdermal methimazole in a PLO gel in cats. Six healthy adult cats were assigned to receive 5 mg of methimazole by the i.v., oral, or transdermal routes, in a randomized triple crossover protocol with 1 week washout between doses. Blood samples were taken for high performance liquid chromatography (HPLC) determination of serum methimazole, at 0, 5, 15, 30, 60 min, and 2, 4, 6, 12 and 24 h after dosing. Methimazole absorption following transdermal administration was poor and variable, with only two of six cats achieving detectable serum methimazole concentrations at any time point following transdermal administration. Area under the concentration-time curve (AUC), maximum concentration (Cmax), and absolute bioavailability were all significantly lower for the transdermal route (0.39 +/- 0.63 microg h/mL, 0.05 +/- 0.09 microg/mL, and 11.4 +/- 18.7%, respectively) than for either i.v. (7.96 +/- 4.38 microg h/mL, 3.34 +/- 2.00 microg/mL, 100%) or oral routes (2.94 +/- 1.24 microg h/mL, 0.51 +/- 0.15 microg/mL, 40.4 +/- 8.1%). The results of this study indicate generally low to undetectable bioavailability of methimazole in a lecithin/pluronic gel given as a single transdermal dose to healthy cats, although one individual cat did achieve nearly 100% transdermal bioavailability relative to the oral route.

The Tissue-Specific Toxicity of Methimazole in the Mouse Olfactory Mucosa Is Partly Mediated through Target-Tissue Metabolic Activation by CYP2A5

“…A HPLC-UV protocol was established, based on a method described previously (Hoffman et al, 2002), for the determination of plasma concentrations of MMZ. An Agilent model 1100 (Agilent Technologies, Santa Clara, CA) HPLC system with a diode array UV detector was used.…”

Pluronic lecithin organogel as a topical drug delivery system

“…The pluronic lecithin organogel was prepared (Hoffman et al, 2002) at room temperature by first taking the specified amount of soybean lecithin in isopropyl palmitate (IPP) used as dispersing, emulsifying, and stabilizing agent (Willimann & Luisi, 1991) and then keeping the mixture overnight for complete dissolution of lecithin. In this sorbic acid was added as preservative.…”

Organogels in Drug Delivery: A Special Emphasis on Pluronic Lecithin Organogels

“…Some in vivo studies have revealed the ability of PLO gels to be excellent drug carriers with penetration enhancement ability. Significant drug penetration into the systemic circulation was observed on repeated topical application of methimazole to the inner pinna of healthy cats suffering from hyperthyroidism, which was not observed after a single application (67). This was assumed to be a consequence of lowered resistance to the drug penetration caused by the exfoliation of stratum corneum produced by the lecithin component in the gel (62).…”