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.