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

Abstract

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.