Plasma pharmacokinetics of morphine after i.m., extradural and intrathecal administration

Eighteen patients received morphine 0.2 mg kg-1 in 0.9% saline i.m. (n = 6), extradurally (n = 6), or in a 10% dextrose solution intrathecally (n = 6) for pain relief operation. Plasma unmetabolized morphine was isolated by extraction using liquid-solid chromatography and measured by radioimmunoassay. Conjugated morphine was calculated from the difference between total immunoreactive morphine and unmetabolized morphine. Initial vascular absorption was significantly less in the intrathecal group than in the i.m. and extradural groups. This accounts for persistence of plasma unmetabolized morphine at 24 h and for more prolonged analgesia in the intrathecal group. Prolonged analgesia observed following extradural and intrathecal administration was caused by a small quantity of unmetabolized morphine. Extradural and i.m. groups showed the same pharmacokinetic patterns although extradural analgesia is much more prolonged. Morphine glucuronide appeared later in blood in the intrathecal group than in the two other groups.