Relative bioavailability of controlled-release oral morphine sulfate during naltrexone blockade.
The effect of naltrexone hydrochloride on the bioavailability of 60 mg controlled-release oral morphine sulfate in normal volunteers was determined using a randomized, 2-way crossover, analytically blinded study design. Although naltrexone did not qualitatively alter the concentration-time curve for controlled-release morphine, the area under the plasma morphine concentration-time curve from 0-24 h (AUC0-24) was significantly greater (p < 0.01) for morphine given with naltrexone (265 ng x h/ml) than for morphine given alone (215 ng x h/ml). Compared to morphine given alone, the apparent absorption half-life of morphine was decreased from 0.94-0.58 h (p = 0.01) and Cmax was increased from 28.17 ng/ml to 32.26 ng/ml (p = 0.04) during naltrexone blockade, whereas the Tmax and apparent elimination half-life of morphine were not significantly affected. The minimal differences in morphine bioavailability indicate naltrexone may be useful in comparative bioavailability studies of high-dose opioids in opioid-naive normal volunteers.
U.S. Food and Drug Administration, Rockville, MD, USA.
E D
ED
Bashaw
R F
RF
Kaiko
R P
RP
Grandy
R F
RF
Reder
P D
PD
Goldenheim
D000328:Adult; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D009271:Naltrexone / Q000009:adverse effects / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D009294:Narcotics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011674:Pulse / Q000187:drug effects; D012119:Respiration / Q000187:drug effects; D016037:Single-Blind Method
D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D009294:Narcotics; D009271:Naltrexone; D009020:Morphine