The influence of the route of administration: a comparative study at steady state of oral sustained release morphine and morphine sulfate suppositories

Steady state pharmacokinetics of morphine (M), morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were investigated in 6 patients with intr actable cancer pain administered orally with MST Mundipharma Limburg, Germa ny) and, subsequently, rectally with MSR to make a judgment whether orally administered morphine can be replaced by rectally administered morphine. Th e parent drug and glucuronide metabolites were measured simultaneously usin g high-performance liquid chromatography (HPLC) and native fluorescence det ection. The mean morphine area under the curve (AUC) value (0-8 h) was smal ler (434.3 +/- 170.2 nmolL(-1)h) in the oral administration than in the rec tal administration (574.8 +/- 285.0 nmolL(-1)h) (p < 0.05). The rectal admi nistration resulted in less production of M3G and M6G. There were no signif icant differences in the mean steady state concentrations (C-ss) of morphin e, M3G, and M6G between the oral and rectal administrations (p > 0.05). The median AUC ratio-M3G/M and M6G/M, 12.58 and 1.85-following MSR rectal admi nistration was smaller than following MST oral administration in 6 patients (19.97 and 2.59; p < 0.05), whereas the median AUC ratio M3G/M6G in the re ctal dosing was 6.24 (range 5.2-7.6) was almost the same as the median rati o M3G/M6G in the oral dosing was 6.49 (range 5.8-8.5, p > 0.1). Four of the 6 patients had a greater C-max of M3G and k16G after oral administration t han after rectal administration, The same 4 had lower fluctuation rates for morphine, M3G (p < 0.05), and M6G (p < 0.05) after metal administration. T herefore, during chronic morphine treatment, it still seems difficult to de cide whether oral administration can be replaced by rectal administration.