The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Oct 1978
Comparative Study Clinical Trial Controlled Clinical TrialAnalgesic studies of codeine and oxycodone in patients with cancer. I. Comparisons of oral with intramuscular codeine and of oral with intramuscular oxycodone.
The relative analgesic potency of oral and intramuscular codeine was evaluated in a double-blind crossover comparison of graded single doses in patients with chronic pain due to cancer. When both duration and intensity of analgesia are considered (total effect), oral codeine was 6/10 as potent as the intramuscular form. ⋯ Like codeine, oxycodone retained at least 1/2 of its analgesic activity when administered orally. We hypothesize that the high oral/parenteral relative potency ratios of codeine and oxycodone relative to morphine and its congeners are not due to more efficient absorption after oral administration, but rather that methylation at position 3 in codeine and oxycodone protects these drugs from rapid first-pass metabolism.
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J. Pharmacol. Exp. Ther. · Oct 1978
Comparative Study Clinical Trial Controlled Clinical TrialAnalgesic studies of codeine and oxycodone in patients with cancer. II. Comparisons of intramuscular oxycodone with intramuscular morphine and codeine.
The relative analgesic potency of single graded intramuscular doses of oxycodone and morphine was evaluated in a double-blind study in patients with chronic pain due to cancer. When both intensity and duration of analgesia are considered (total analgesic effect), oxycodone was 2/3 to 3/4 as potent as morphine, while in terms of peak analgesia, it was 8/10 to equipotent. In doses producing equivalent peak effect, oxycodone had a shorter duration of action than morphine. ⋯ In terms of total analgesic effect, oxycodone was 10 times as potent as codeine, while in terms of peak analgesia it was 12 times as potent. These relative potency relationships of oxycodone, taken in conjunction with the oral/parenteral potency ratios of codeine and oxycodone established in the previous paper and several previous relative potency assays involving morphine, oxymorphone and codeine, demonstrate a highly consistent pattern of analgesic structure-activity relationships encompassing morphine, oxymorphone, codeine and oxycodone. The results of these studies do not appear to support the hypothesis that, in man, the analgesic activity of codeine is due to its O-demethylation to morphine.