Repeated Dose Relative Potency Studies

Relative potency estimates derived from single-dose studies may not be sufficient to predict chronic dosing requirements, particularly when the pharmacokinetics of the treatments and their active metabolites differ. For example, the slowly-metabolized analgesic methadone is equipotent to morphine as a single parenteral dose (Beaver et al., 1967) However, observations in cancer patients being converted from chronic treatment with one drug to the other suggest that if one doses repeatedly for the week or so required to attain methadone’s steady state, a given dose of methadone is more than ten times as potent as morphine (Lawlor et al., 1998). Repeated dose relative potency studies of the common opioid analgesics are needed to provide a better basis for clinical treatment.

Problem 6.4

You are asked to review data on the relative potency of sustained-release morphine and transdermal fentanyl. The subjects were 30 patients who have been stabilized on a dose of sustained-release morphine that reflected the patient’s preferred balance of pain relief and side effects and required no more than two doses per day of immediate-release rescue hydromorphone. They were then switched to transdermal fentanyl, starting with a conversion of 25 mcg/hr fentanyl for every 90 mg/day of sustained-release morphine. The fentanyl dose was again titrated every two days until the patient indicated that the dose seemed optimal and no more than two rescue doses per day were needed. The fentanyl titration took an average of two weeks and the final drug doses, rescue doses, and pain levels were:

The investigators concluded that the relative potency of these two preparations is 5 mg/day morphine for every 1 mcg/hr transdermal fentanyl.

Are the following critiques of these conclusions true or false?

Question 6.4.1

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