The lipid solubility and degree of ionization of morphine plays an important party in both the onset and duration of analgesia and the CNS effects. At this pH, the tertiary amino group in each of the opioids is mostly ionized, making the molecule water soluble. Morphine, with additional hydroxyl groups on the molecule, is significantly more water soluble than any other opioid in clinical use. Morphine, injected into the epidural space, is rapidly absorbed into the general circulation. Absorption is so rapid that the plasma concentration-time profiles closely resemble those obtained after intravenous or intramuscular administration.
Plasma concentrations decline in a multiexponential fashion.
CSF concentrations of morphine, after epidural doses of 2 to 6 mg in postoperative patients, have been reported to be 50 to 250 times higher than corresponding plasma concentrations. The CSF levels of morphine exceed those in plasma after only 15 minutes and are detectable for as long as 20 hours after the injection of 2 mg of epidural morphine. This corresponds to the relative minimum effective epidural and intrathecal doses of 5 mg and 0.25 mg, respectively. Maximum CSF concentrations are seen 60-90 minutes after injection. The intrathecal route of administration circumvents meningeal diffusion barriers and, therefore, lower doses of morphine produce comparable analgesia to that induced by the epidural route.