UI - 000048

AU - Wallenstein SL

AU - Kaiko RF

AU - Rogers AG

AU - Houde RW

TI - Crossover trials in clinical analgesic assays: studies of buprenorphine and morphine

AB - Analgesic studies of buprenorphine, a thebaine derivative and potent partial narcotic agonist, were

carried out in patients with cancer who had postoperative or chronic pain. Intramuscular buprenorphine was

compared with intramuscular morphine in a series of sequentially related, twin crossover assays and was

found to be about 25 times as potent as morphine. Side effects were essentially morphine-like. In a second

assay, the acceptability and analgesic activity of sublingual buprenorphine was studied in a 6-dose, balanced,

incomplete block assay, a modification of the twin crossover design employed in the all-intramuscular trial.

Sublingual buprenorphine was found to be about 15 times as potent as intramuscular morphine and was well

accepted by our patients. The 4-dose twin crossover trial in which doses are adjusted sequentially is more

flexible in that a wide range of doses may be studied, but it lacks the ability of the 6-dose design to provide

estimates of the curvature of the dose-response slopes of the study drugs. When first-dose-only data were

analyzed as parallel group assays, the main difference in results compared with the crossover studies was a

decrease in efficiency and sensitivity

SO - Pharmacotherapy 1986;6:228-235