Pharmacokinetics of subcutaneous and intravenous bolus doses of morphine in palliative care cancer patients receiving infusion of morphine: A pharmacokinetic substudy of a randomized controlled trial

Aims To compare the pharmacokinetics of intravenous (IV) and subcutaneous (SC) morphine bolus doses in palliative care patients receiving patient‐controlled analgesia. Methods This pharmacokinetic substudy of a double‐blinded, randomized controlled trial included 20 patients with advanced cancer requiring morphine infusion. After 20–48 h of patient‐controlled analgesia, a baseline blood sample was drawn before bolus administration, followed by 16 samples over 2 h. Time to maximum concentration, maximum concentration and area under the curve to 60 min (AUC0–60) were determined. Group differences were assessed using linear mixed‐effects modelling. Results Median (Q1, Q3) time to maximum concentration was significantly shorter for IV (2 [2, 2] min) compared to SC (10 [5, 15] min, P < .001). Dose‐adjusted maximum concentration was 3 times higher in the IV group. Linear mixed‐effects modelling showed on average, significantly higher serum concentrations for IV during the 0–60 min period postbolus, although differences in AUC0–60 were not statistically significant (mean AUC0–60: SC, 7621 nmol min/L [95% confidence interval: 5714–10 163]; IV, 9382 nmol min/L [95% confidence interval: 5914–14 884]). At steady state, higher infusion rates were associated with markedly higher concentrations in the IV group. Low albumin correlated with higher serum morphine concentrations. No differences in respiratory rates or sedation were observed. Conclusions IV morphine showed faster absorption with substantially higher peak concentrations compared to SC. Further research is needed to assess the clinical relevance of these differences.