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Cutaneous morphine provides poor pain relief.

BOSTON -- Morphine is a poor candidate for transdermal drug delivery, Judith Paice, Ph.D., said at the annual meeting of the American Academy of Hospice and Palliative Medicine.

Dr. Paice said she and her colleagues conducted a small study to assess the bioavailability of a topical formulation of morphine relative to the 100% bioavailable subcutaneous dose, but in blood samples collected from the participants beginning 5 minutes to 10 hours after dose administration "we seldom detected morphine in plasma samples after topical administration, and when it was detected, the concentrations were below the limit of quantification [0.5 ng/ml]."

The minimum effective analgesic plasma morphine concentrations are 10 ng/ ml or higher, she noted.

In the first arm of their placebo-controlled, double-blind, crossover study, the investigators randomly assigned five healthy volunteers to receive either 1 mL of morphine compounded at 10 mg/mL in a pluronic lecithin organogel (PLO) base applied to the wrist and 1 mL of subcutaneous saline or 1 mL of topical drug-free PLO base and 1 mL (3 mg/mL) of subcutaneous morphine.

Each participant received the opposite combination in the second arm of the study, Dr. Paice said. A total of 17 blood samples were collected during the 5-minute to 10-hour period after administration.

Dr. Paice undertook the study after hospice workers told her about an "amazing" morphine gel they were rubbing on the wrists of patients in place of more expensive fentynal patches.

"I was bothered by this [report] because, if one has any knowledge of pharmacology, they know morphine is a hydrophilic compound. It is not lipid-soluble to the degree that fentanyl is, which is why we have a fentanyl transdermal patch and not a morphine transdermal patch," she said.

An initial literature review resulted in some small case series. One included six patients who purportedly had localized pain relief.

Another included three patients with ulcers and burns, who are more likely to show some benefit because morphine can access the local circulation when the skin's barrier has been broken down. In cadaver and animal studies, only a fraction of topically administered morphine was absorbed through the skin, she said.

The current study finding is disappointing for those working in palliative care, where patients are likely to have swallowing difficulties or intestinal obstructions that preclude oral administration of medications, said Dr. Paice, director of the Cancer Pain Program at Northwestern University in Chicago.

It also is troubling, because morphine in a topically administered gel "'is being promoted as an alternative analgesic option without the evidence to support it," she added.


Major Finding: Subcutaneous morphine was 100% bioavailable in plasma samples taken between 5 minutes to 10 hours after administration, but a topical morphine formulation was seldom detected, and when it was, concentrations were below the limit of quantification (0.5 ng/mL).

Data Source: A placebo-controlled, double-blind, crossover study of five healthy volunteers randomized to topical or subcutaneous morphine.

Disclosures: The study was supported by a grant from the palliative medication management company excelleRx Inc. The researcher had no other relevant financial disclosures.
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Title Annotation:PALLIATIVE CARE
Comment:Cutaneous morphine provides poor pain relief.(PALLIATIVE CARE)
Author:Mahoney, Diana
Publication:Family Practice News
Article Type:Report
Geographic Code:1USA
Date:Apr 15, 2010
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