Epidural and intrathecal opiates: cerebrospinal fluid and plasma profiles in patients with chronic cancer pain.

We studied the cerebrospinal fluid (CSF) and plasma concentration-time profiles of morphine, methadone, and beta-endorphin after lumbar epidural or intrathecal injection in 17 patients with cancer. After epidural injection, all three drugs reached peak levels in lumbar CSF within 34 minutes that were 50 to 1300 times higher than free drug concentrations in plasma. The rate of decline of CSF levels correlated with drug lipid solubility (methadone [t1/2 = 73 minutes] greater than morphine [126 minutes] greater than beta-endorphin [317 minutes]). Plasma levels were comparable with those after intragluteal injection of the same dose. In four patients given intrathecal morphine or methadone, CSF at the C1-2 level contained high levels of morphine as early as 1 hour after injection, but levels of methadone were lower or undetectable. Three of 17 patients reported improved analgesia initially, but none were improved at 2 weeks after chronic therapy. We conclude that analgesia induced by intrathecal or epidural morphine injections is caused by drug acting at both spinal and supraspinal sites. The use of spinal opiates such as morphine is of limited value in patients whose pain is not adequately managed by high systemic doses of morphine-like drugs.