Morphine pharmacokinetics and molecular data

List of indications
Distribution Clearance Minimum analgesic

Distribution
Morphine has an apparent volume of distribution ranging from 1 to 4.7 L/kg after intravenous dosage. Protein binding is low, about 36%, and muscle tissue binding is reported as 54%. When morphine is introduced outside of the CNS, plasma concentrations of morphine remain higher than the corresponding CSF morphine levels.

Clearance
Morphine has a total plasma clearance which ranges from 0.9 to 1.2 L/kg/h (liters/kilogram/hour) in postoperative patients, but shows considerable interindividual variation. The major pathway of clearance is hepatic glucuronidation to morphine-3-glucuronide, which is pharmacologically inactive. The major excretion path of the conjugate is through the kidneys, with about 10% in the feces. Morphine is also eliminated by the kidneys, 2 to 12% being excreted unchanged in the urine. Terminal half-life is commonly reported to vary from 1.5 to 4.5 hours, although the longer half-lives were obtained when morphine levels were monitored over protracted periods with very sensitive radioimmunoassay methods. The accepted elimination half-life in normal subjects is 1.5 to 2 hours.

Minimum analgesic
The minimum analgesic morphine plasma concentration during Patient-Controlled Analgesia (PCA) has been reported as 20-40 ng/mL, corresponding to a self-administration rate of 1.5 to 3 mg/h.