Single-dose and steady-state kinetics of morphine and its metabolites in cancer patients--a comparison of two oral formulations.
The single-dose and steady state kinetics of morphine given as controlled-release tablets (30 mg every 12 h) and as a solution (15 mg every 6 h) have been compared in 11 cancer patients with chronic pain. The concentrations of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) were analyzed by HPLC. There were no significant differences between the tablets and solution in the mean steady state concentrations of morphine, M3G or M6G. The tmax was 3.3 h for the tablets compared to 1.1 h for the solution. After giving the controlled-release tablets every 12 h there was a significantly higher fluctuation index of the morphine concentrations than after the solution. Urinary recovery at steady state was comparable between the two preparations, with averages of 57% and 47%, respectively. Thus, no major differences were found in the pharmacokinetics of morphine and its glucuronidated metabolites after 30 mg morphine as controlled-release tablets every 12 h or 15 mg of morphine solution every 6 h, except for a significantly longer tmax and greater fluctuation in morphine concentrations after the controlled-release tablets.
Hasselström
J
J
Department of Clinical Pharmacology, Huddinge University Hospital, Karolinska Institute, Sweden.
Alexander
N
N
Bringel
C
C
Svensson
J O
JO
Säwe
J
J
D000230:Adenocarcinoma / Q000378:metabolism; D000284:Administration, Oral; D000368:Aged; D018288:Carcinoma, Small Cell / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D003692:Delayed-Action Preparations; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D009022:Morphine Derivatives / Q000032:analysis* / Q000097:blood; D009369:Neoplasms / Q000378:metabolism*; D012996:Solutions; D013607:Tablets
D003692:Delayed-Action Preparations; D009022:Morphine Derivatives; D012996:Solutions; D013607:Tablets; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide