Biomaterial Database

Morphine and morphine metabolite concentrations in cerebrospinal fluid and plasma in cancer pain patients after slow-release oral morphine administration. 1995

Tomas Wolff, and Håkan Samuelsson, and Thomas Hedner

Pain Sections, Department of Anaesthesia, Central Hospitals, Skövde and Borås, Sweden Department of Clinical Pharmacology, Sahlgrenska University Hospital, Göteborg, Sweden.

In 34 cancer patients treated with chronic slow-release oral morphine, plasma and cerebrospinal fluid (CSF) minimum steady-state concentrations of morphine (M), morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were determined by high-performance liquid chromatography (HPLC). Both plasma and CSF morphine, M3G and M6G, concentrations were linearly related to dose of morphine. At steady state, the mean +/- SEM CSF/plasma morphine concentration ratio was 0.8 +/- 0.1. In plasma and CSF, the mean steady-state concentrations of M3G and M6G substantially exceeded those of morphine where the mean CSF M/M3G/M6G ratio was 1:47:5 (weight basis), 1:34:4 (molar basis) and the mean plasma ratio was M/M3G/M6G 1:150:23 (weight basis), 1:109:17 (molar basis). The mean M3G and M6G concentrations in CSF at steady state were 15-18% of those found in plasma. Pain relief, evaluated by a visual analogue scale (VAS), did not correlate with the CSF M3G concentrations or with the M3G/M ratio. Since CSF M6G concentrations were high, M6G could, however, contribute to pain relief. We conclude that after oral administration of slow-release morphine, there is a significant passage of the morphine glucuronide metabolites to the CSF and that the M3G and M6G metabolites in CSF are in the concentration range where they may have an influence on analgesia.

UI	MeSH Term	Description	Entries
D008161	Lumbosacral Region	Region of the back including the LUMBAR VERTEBRAE, SACRUM, and nearby structures.	Lumbar Region,Lumbar Regions,Lumbosacral Regions,Region, Lumbar,Region, Lumbosacral,Regions, Lumbar,Regions, Lumbosacral
D009020	Morphine	The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.	Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D009022	Morphine Derivatives	Analogs or derivatives of morphine.	Morphines
D009369	Neoplasms	New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D010146	Pain	An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.	Suffering, Physical,Ache,Pain, Burning,Pain, Crushing,Pain, Migratory,Pain, Radiating,Pain, Splitting,Aches,Burning Pain,Burning Pains,Crushing Pain,Crushing Pains,Migratory Pain,Migratory Pains,Pains, Burning,Pains, Crushing,Pains, Migratory,Pains, Radiating,Pains, Splitting,Physical Suffering,Physical Sufferings,Radiating Pain,Radiating Pains,Splitting Pain,Splitting Pains,Sufferings, Physical
D003692	Delayed-Action Preparations	Dosage forms of a drug that act over a period of time by controlled-release processes or technology.	Controlled Release Formulation,Controlled-Release Formulation,Controlled-Release Preparation,Delayed-Action Preparation,Depot Preparation,Depot Preparations,Extended Release Formulation,Extended Release Preparation,Prolonged-Action Preparation,Prolonged-Action Preparations,Sustained Release Formulation,Sustained-Release Preparation,Sustained-Release Preparations,Timed-Release Preparation,Timed-Release Preparations,Controlled-Release Formulations,Controlled-Release Preparations,Extended Release Formulations,Extended Release Preparations,Slow Release Formulation,Sustained Release Formulations,Controlled Release Formulations,Controlled Release Preparation,Controlled Release Preparations,Delayed Action Preparation,Delayed Action Preparations,Formulation, Controlled Release,Formulations, Controlled Release,Prolonged Action Preparation,Release Formulation, Controlled,Release Formulations, Controlled,Sustained Release Preparation,Timed Release Preparation,Timed Release Preparations
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000284	Administration, Oral	The giving of drugs, chemicals, or other substances by mouth.	Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000701	Analgesics, Opioid	Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.	Opioid,Opioid Analgesic,Opioid Analgesics,Opioids,Full Opioid Agonists,Opioid Full Agonists,Opioid Mixed Agonist-Antagonists,Opioid Partial Agonists,Partial Opioid Agonists,Agonist-Antagonists, Opioid Mixed,Agonists, Full Opioid,Agonists, Opioid Full,Agonists, Opioid Partial,Agonists, Partial Opioid,Analgesic, Opioid,Full Agonists, Opioid,Mixed Agonist-Antagonists, Opioid,Opioid Agonists, Full,Opioid Agonists, Partial,Opioid Mixed Agonist Antagonists,Partial Agonists, Opioid