RELATIVE BIOAVAILABILITY OF CONTROLLED RELEASE MORPHINE TABLETS (MST CONTINUS) IN CANCER PATIENTS

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Abstract
The bioavailability of oral controlled release morphine tablets (MST, Napp Laboratories) and oral morphine sulphate in aqeuous solution (MSS) was compared in 10 patients with advanced cancer. Serum samples were analysed for morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) using a specific HPLC assay. The relative bioavailability of morphine with MST was significantly less than that with MSS (mean 80%, range 50-110%) although there was no difference between the formulations in the relative availability of M3G and M6G. There was no significnt difference between the formulations in the serum concentration of morphine at 12 h. The mean ratios morphine: M6G:M3G (comparing areas under the serum concentration-time curves) were 1:9:56. There was a highly significant linear relationship between the dose administered and AUC for morphine, M3G and M6G after MSS; and for morphine after MST. Median tmax for morphine was 0.5 h with MSS and 2.5 h with MST; for M3G 1.5 h with MSS and 3.0 h with MST; and for M6G 1.5 h with MSS and 3.25 h with MST. A secondary peak of unconjugated morphine, which may represent enterohepatic circulation, was seen in several patients 2-4 h after administration of elixir and 4-6 h after administration of MST.