Evaluation of methadone absorption after topical administration to hospice patients

Increased use of methadone (MTD) applied topically as an extemporaneously compounded gel was documented on routine review of medication profiles of hospice patients. A literature search did not identify any published clinical studies assessing the systemic absorption or clinical efficacy of MTD administered topically to intact skin for systemic pain.

To compare serum MTD levels achieved after topical and oral administration to hospice patients.

To assess the absorption of MTD administered topically, two steady-state serum levels were determined in 10 patients administered MTD topically (10-45 mg/day as powder dissolved in ethoxydiglycol added to the calculated volume of pluronic lecithin organogel [PLO]), five patients administered MTD orally (PO) (15-40 mg/day), and one subject administered placebo topically.

MTD levels from the subject administered placebo were <10 ng/mL. Eighteen of 20 serum MTD concentrations from nine patients administered topical MTD were identical to those in the placebo control. Only one of 10 patients administered topical MTD achieved measurable serum MTD levels. This patient was on the highest topical dose administered (45 mg/day) and achieved a mean serum concentration of 25.8 ng/mL (18-35 ng/mL). All MTD serum concentrations from patients administered oral MTD exceeded the lower limit of the reference range (10 ng/mL). The range of concentrations in the oral group ranged from 62 to 393 ng/mL (mean=150.9 ng/mL).

The topical application of an MTD-PLO gel in doses <45 mg/day did not result in trough MTD serum concentrations associated with analgesia. An observer placebo response may explain the perceived benefit of MTD applied topically as a PLO gel in doses <45 mg/day. The evaluation of systemic absorption of MTD-PLO gel in doses >45 mg/day is warranted.