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The Disposition and Cerebrospinal Fluid Penetration of Morphine and Its Two Major Glucuronidated Metabolites in Adults Undergoing Lumbar Myelogram
Author(s) -
Laizure S. Casey,
Miller Joseph H.,
Stevens Robert C.,
Donahue David J.,
Laster Robert E.,
Brown Donna
Publication year - 1993
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1993.tb04309.x
Subject(s) - morphine , pharmacokinetics , medicine , cerebrospinal fluid , opiate , anesthesia , lumbar , volume of distribution , urine , analgesic , pharmacology , surgery , receptor
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.