The Disposition and Cerebrospinal Fluid Penetration of Morphine and Its Two Major Glucuronidated Metabolites in Adults Undergoing Lumbar Myelogram

STUDY OBJECTIVE: To determine the pharmacokinetic disposition of morphine and its two major glucuronidated metabolites, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G), in serum and their penetration into cerebrospinal fluid (CSF). DESIGN: A single-dose, open-label pharmacokinetic study. SETTING: The Memphis Neurosciences Center at Methodist Hospital. PATIENTS: Twenty patients undergoing a diagnostic lumbar myelogram. INTERVENTIONS: All patients received morphine sulfate 10 mg intramuscularly approximately 1.5 hours before the procedure. MEASUREMENTS AND MAIN RESULTS: Three blood samples were drawn after the dose and a CSF sample was drawn immediately after lumbar puncture. The mean +/- standard deviation for the half-life of morphine was 2.8 +/- 1.4 hours. The apparent half-lives of M6G and M3G were 5.7 +/- 3.1 and 6.3 +/- 2.2 hours, respectively, and were inversely related to the estimated creatinine clearance (r = -0.61, p < 0.007 and r = -0.69, p < 0.002, respectively). The mean concentrations of morphine, M6G, and M3G in the CSF (collection time 1.5 +/- 0.32 hrs, n = 19) were 3.1 +/- 3.7, 12.5 +/- 17.6, and 19.6 +/- 16.1 nmol/L, respectively. CONCLUSIONS: Elderly patients and patients with renal dysfunction receiving morphine may experience prolonged analgesic and adverse effects secondary to a decrease in the clearance of M6G.