title: Distinct relations among plasma concentrations required for different pharmacological effects in oxycodone, morphine, and fentanyl.
abstract: Several clinical reports showed that adverse effect profiles are not the same in morphine, oxycodone, and fentanyl. The authors investigated whether the relationship between plasma concentrations for antinociceptive effect and for various pharmacological effects differed among oxycodone, morphine, and fentanyl under controlled experimental setting using animal models. Oxycodone induced constipation and an antinociceptive effect in a similar concentration-dependent manner, whereas morphine required approximately 9-fold higher plasma concentration for antinociceptive effect compared with that for constipation when 50% effective plasma concentration (EC(50)) levels were compared. The EC(50) values for inhibition of behavioral activity were 2.1-, 2.7-, and 1.3-fold higher than those for antinociceptive effect in oxycodone, morphine, and fentanyl, respectively. Respiratory inhibition was observed even at higher plasma concentrations in all three opioids, and the differences in the EC(50) values compared with those for antinociceptive effects were 234.5-fold (oxycodone), 233.1-fold (morphine), or 104.2-fold (fentanyl). These results showed that oxycodone, morphine, and fentanyl exhibited unique patterns of plasma concentrations required for different pharmacological effects. The different adverse effect profiles observed in a clinical setting appear to be resulted from, at least in part, distinct intrinsic pharmacological profiles among these μ-opioid receptor agonists.
authors: Medicinal Research Laboratories, Shionogi & Co., Ltd., Shiga, Japan.
authors: Atsushi
authors: A
authors: Nakamura
authors: Minoru
authors: M
authors: Hasegawa
authors: Hisanori
authors: H
authors: Ito
authors: Kazuhisa
authors: K
authors: Minami
authors: Katsumi
authors: K
authors: Koike
authors: Naoko
authors: N
authors: Habu-Tomita
authors: Kenkichi
authors: K
authors: Nanba
authors: Kayo
authors: K
authors: Hamaguchi
authors: Eriko
authors: E
authors: Noshi
authors: Hiroshi
authors: H
authors: Hashimoto
authors: Ikuko
authors: I
authors: Nishino
authors: Yoshito
authors: Y
authors: Okabayashi
authors: Kiyotaka
authors: K
authors: Koyabu
authors: Tsuyoshi
authors: T
authors: Kihara
authors: Yuka
authors: Y
authors: Iwamoto
authors: Yuji
authors: Y
authors: Inoue
authors: Minoru
authors: M
authors: Narita
authors: Tsutomu
authors: T
authors: Suzuki
authors: Akira
authors: A
authors: Kato
mesh_terms: D000700:Analgesics / Q000097:blood / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000097:blood* / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects; D003248:Constipation / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000009:adverse effects / Q000097:blood* / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D009020:Morphine / Q000009:adverse effects / Q000097:blood* / Q000494:pharmacology; D010098:Oxycodone / Q000009:adverse effects / Q000097:blood* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D009020:Morphine; D010098:Oxycodone; D005283:Fentanyl