Cerebrospinal Fluid and Plasma Concentrations of Morphine, Morphine-3-Glucuronide, and Morphine-6-Glucuronide in Patients Before and After Initiation of Intracerebroventricular Morphine for Cancer Pain Management

In vivo profiling of seven common opioids for antinociception, constipation and respiratory depression: no two opioids have the same profile

“…Deaths due to opioid overdose are almost always due to respiratory depression (Francisco, ), making respiratory depression the most serious adverse effect associated with the use of opioid analgesics (Reisine and Pasternak, ; Otis, ). In patients given morphine by systemic routes, metabolically derived M6G crosses the blood–brain barrier (Carrupt et al ., ; Bourasset et al ., ), resulting in mean steady‐state CSF M6G concentrations that are ∼12% of the corresponding plasma concentrations (Smith et al ., ). As metabolically derived M6G has the potential to induce respiratory depression, caution is required in patients with renal impairment as M6G will accumulate in the systemic circulation and the CSF, increasing the likelihood of M6G‐induced respiratory depression at usual morphine doses (Wright et al ., ; South et al ., ).…”

Pharmacokinetic modelling of morphine, morphine-3-glucuronide and morphine-6-glucuronide in plasma and cerebrospinal fluid of neurosurgical patients after short-term infusion of morphine

“…The fraction of the dose converted to each metabolite was kept constant for all patients (M3G 0.55, M6G 0.1). of active transport or facilitated diffusion into the CSF has been discussed [30][31][32], but remain to be established. The fact that CSF concentrations were better described by saturable transport seemed to exclude simple diffusion as the main mechanism of entry into the CSF.…”

“…Regular analgesia was stopped during this interval. Blood samples (4 ml) were taken from an indwelling venous catheter before and 3,15,30,60,120,180,240,360,480,720,960,1200,1440,1920, 2880 min after the start of morphine infusion.…”

“…CSF, obtained under strictly sterile conditions from the ventricular catheter using a 2 ml syringe, was taken before and 15,30,60,120,240,360,480,720,960,1200,1440,1920, 2880 min after the start of the morphine infusion.…”

Pharmacokinetic modelling of morphine, morphine‐3‐glucuronide and morphine‐6‐glucuronide in plasma and cerebrospinal fluid of neurosurgical patients after short‐term infusion of morphine

“…The permeability of the morphine glucuronides through the blood–brain barrier is believed to be even poorer than that of M based on animal data [29] and this is reflected in our results. Possible mechanisms of active transport or facilitated diffusion into the CSF has been discussed [30–32], but remain to be established. The fact that CSF concentrations were better described by saturable transport seemed to exclude simple diffusion as the main mechanism of entry into the CSF.…”