Related Experiment Video

Updated: Oct 20, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
07:23

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

Published on: July 29, 2014

Morphine and morphine-6-glucuronide in the plasma and cerebrospinal fluid of children

R D Hain1, A Hardcastle, C R Pinkerton

  • 1Departments of Paediatric Oncology and Palliative Care, Llandough and Community NHS Trust, Penlan Road, Cardiff CF64 2XX, UK.

British Journal of Clinical Pharmacology
|June 26, 1999
PubMed

Insights

Children with cancer extensively metabolize morphine to morphine-6-glucuronide (M6G). This study measured morphine and M6G in pediatric plasma and cerebrospinal fluid, highlighting M6G

Area of Science:

  • Pediatric pharmacology
  • Pharmacokinetics
  • Cancer pain management

Background:

  • Morphine is a common analgesic in children.
  • Understanding morphine metabolism is crucial for safe and effective pain management.
  • Morphine-6-glucuronide (M6G) is an active metabolite with potential for accumulation.

Purpose of the Study:

  • To quantify morphine and M6G concentrations in pediatric plasma and cerebrospinal fluid (CSF).
  • To characterize the pharmacokinetics of morphine and M6G in children with leukemia.
  • To compare morphine and M6G passage into the CSF of children versus adults.

Main Methods:

  • Collected paired plasma and CSF samples from 29 children with leukemia undergoing lumbar puncture.
  • Administered a single intravenous dose of morphine prior to sample collection.
  • Measured morphine using radioimmunoassay (RIA) and M6G using enzyme-linked immunosorbent assay (ELISA).

Main Results:

  • ELISA for M6G demonstrated high sensitivity and acceptable assay variability.
  • Pediatric morphine pharmacokinetics (elimination half-life, volume of distribution) were comparable to adults, but clearance was higher.
  • Children readily synthesized M6G, which had a significantly longer elimination half-life and higher area under the curve (AUC) in plasma compared to morphine.

Conclusions:

  • Demonstrated extensive morphine metabolism to M6G in pediatric cancer patients.
  • Results support the clinical significance of M6G accumulation with repeated morphine dosing in children.
  • No evidence suggested increased morphine penetration into the CSF of children compared to adults.
Abstract

More Related Videos

A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats04:11

A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats

Published on: November 6, 2018

Intracranial Pharmacotherapy and Pain Assays in Rodents02:26

Intracranial Pharmacotherapy and Pain Assays in Rodents

Published on: April 9, 2019

Related Concept Videos

Opioid Analgesics: Morphine and Other Natural Cogeners01:20

Opioid Analgesics: Morphine and Other Natural Cogeners

Opioids are a class of drugs that mimic endogenous opioid peptides and act on opioid receptors, and help in pain relief. These compounds are classified as natural, synthetic, or semi-synthetic. Natural opioids, like morphine, codeine, and thebaine, are derived from the opium poppy plant (Papaver somniferum or Papaver album) and are termed opiates. Synthetic opioids are artificial, while semi-synthetic opioids combine natural and synthetic compounds. Morphine, a prototypical opioid, possesses a...
Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses a challenge in...
Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption01:23

Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption

Understanding the physiological differences in the pediatric population is crucial for effective pharmacotherapy. Neonates, infants, and children exhibit significant variations in gastric pH, gastric emptying time, intestinal transit time, and biliary function. These variations profoundly affect oral drug absorption, necessitating a nuanced approach to pediatric dosing.Neonates present with a unique physiological profile, having a gastric pH greater than 4 and faster and more irregular gastric...
Opioid Analgesics: Synthetic and Semisynthetic Opioids01:15

Opioid Analgesics: Synthetic and Semisynthetic Opioids

Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...
Pharmacokinetics in Pediatric Patients: Drug Distribution01:17

Pharmacokinetics in Pediatric Patients: Drug Distribution

Drug distribution in the pediatric population exhibits unique challenges and considerations due to the physiological differences between children, particularly neonates and infants, and adults. A crucial aspect of pediatric pharmacology is understanding how these differences impact the pharmacokinetics of various drugs, necessitating age-specific dosing strategies to ensure efficacy and safety.Neonates and infants have a higher total body water content, ~75%–90% of their body weight, compared...
Pharmacokinetics in Pediatric Patients: Drug Excretion01:26

Pharmacokinetics in Pediatric Patients: Drug Excretion

In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...