Pharmacokinetics of epidural morphine in man

Abstract

Cerebrospinal fluid (CSF) and plasma morphine concentrations were determined in 5 patients after epidural administration of 6 mg morphine; plasma samples were collected frequently during the initial 6 h and 6-7 CSF samples were obtained from each patient over a 24 h period. Morphine was analysed using gas chromatography and electron capture detection. Individual morphine concentration-time curves were plotted for plasma and CSF and various pharmacokinetic variables were calculated. Plasma morphine concentrations after epidural injection were similar to those found after intramuscular administration; Cmax (66 +/- 8 mg/ml: mean +/- SEM) appeared within 12 +/- 3 min, and the terminal elimination half-life in plasma was 213 +/- 24 min. In CSF, morphine reached a peak (1575 +/- 359 ng/ml) after 135 +/- 40 min. The terminal elimination half-life for morphine in CSF was 239 +/- 10 min. The CSF bioavailability of morphine after epidural administration was calculated to be 1.9 +/- 0.5%. The study showed that epidural administration of morphine resulted in CSF concentrations many times higher than those in plasma, but still only 2% of the dose administered was available to the CSF compartment. Morphine was eliminated with similar speed from CSF and plasma.

Morphine‐induced depression of spinal excitation is not altered following acute disruption of GABAA or GABAB receptor activity

“…and unmyelinated nerve fibres. Significantly effective doses here were comparable to clinically relevant morphine concentrations achieved 1-2 h after epidural administration (Nordberg et al, 1983(Nordberg et al, , 1984. MOR effectively depressed C fibre-evoked field potentials, but not those evoked jointly by Ab and Ad fibres, which is in line with the well established relative selectivity of spinally applied MOR for noxious input (Le Bars et al, 1976;Sandkü hler et al, 1990).…”

Spinal Opioid Bioavailability in Postoperative Pain

“…On the basis of the all the aforementioned experimental studies, we can deduce that the bioavailability of hydrophilic opioids to the spinal opioid receptors, such as morphine, is higher than that for lipophilic opioids, (alfentanil, sufentanil, or fentanyl). In fact, U.S. Food and Drugs Administration (FDA) have so far only approved hydrophilic opioids (morphine and hydromorphone) as first‐line drugs for spinal use in the context of chronic pain .…”

New Drugs for Epidural Analgesia

“…In relation to the slow passage through the dural membrane, the major CSF morphine levels are reached after 1-2 h prolonging duration of analgesia. The minimal steady state analgesic concentration of morphine in plasma is considered to be 16 ng/ml but when morphine is administered via epidural route its plasmatic concentration lasts above this level for only about 1 h supporting that the main morphine action site is spinal cord [43,44]. Recent clinical practice is going to replace hydrophilic morphine with more lipophilic opioids such as fentanyl and sufentanyl because of their more limited brainstem mediated side effects such as sedation and respiratory depression compared to morphine.…”