Plasma morphine and glucuronide (M3G and M6G) concentrations in hospice inpatients

Plasma morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) concentrations were quantified by high performance liquid chromatography (HPLC) in 36 hospice inpatients receiving morphine orally or subcutaneously. The data were analyzed in relation to dose, serum creatinine, serum gamma glutamyl transferase, and presence or absence of opioid-induced adverse effects. There were significant associations (P < 0.05) between plasma morphine, M3G (subcutaneous route only), and M6G concentrations and dose for both routes of administration. The mean dose-corrected plasma morphine concentration for the subcutaneous group was three times that of the oral group, confirming present oral to subcutaneous dose conversion practices. Nineteen patients experienced symptoms attributed to morphine: nausea and vomiting in ten and acute delirium in nine. Serum creatinine was elevated in patients with adverse effects (P = 0.031), as were the dose-corrected plasma M3G (P = 0.029) and M6G (P = 0.043) concentrations. All seven patients with serum creatinine concentrations above the normal range had symptoms attributed to opioid-induced adverse effects. Plasma M3G, M6G, and dose-corrected plasma M3G and M6G concentrations were significantly (P < 0.001) higher in these patients than in those with normal serum creatinine concentrations. The data indicate that accumulation of M3G and M6G may be a causal or aggravating factor in the nausea and vomiting and cognitive function profile of palliative and terminal care patients with significant renal function impairment.