Morphine clearance in premature neonates increased with post-conceptional age, but no differences were observed in distribution volume among the various groups in terms of post-gestational age.
Again, the behavioral pain response did not correlate with clearance or distribution levels. Anand et al. Br J Anaesth. Clearance increased from 2.
Barret et al. Morphine, morphineglucuronide and morphineglucuronide pharmacokinetics in newborn infants receiving diamorphine infusions. The patients received diamorphine loading followed by infusion over hours. Morphine was detected in the plasma of all subjects. The clearance of morphine, but not its distribution volume, correlated with age.
The morphineglucuronide and morphineglucuronide formation clearances were 2. Moreover, their respective excretion clearances were 0. Thus, the metabolism of morphine in neonates was similar to that in adults, in terms of the respective contributions of each glucuronide pathway. In another study, Pokela et al. Age-related morphine kinetics in infants. Dev Pharmacol Ther. The half-life decreased with age, with the highest value in 10 neonates younger than 1 week, a moderate value in 10 infants aged 1 week, and the lowest value in 7 infants aged from months.
The clearance of morphine increased correspondingly with age but was significantly lower in critically ill infants and it approached adult values after the age of 1 month.
Chay et al. Pharmacokinetic-pharmacodynamic relationships of morphine in neonates. The pharmacokinetic parameters are summarized in Table 2. Morphineglucuronide was not detected in the plasma of any neonate, which may explain why neonates require high plasma concentrations of unchanged morphine for sedation.
Additionally, the half-life, clearance and distribution volumes were not significantly different between preterm and term.
Lynn and Slattery 27 Morphine pharmacokinetics in early infancy. Pharmacokinetic parameters are displayed in Table 2. Infants aged days showed longer elimination half-lives than older infants did 6. The combination of lower clearance and a longer elimination half-life in newborns may well explain the prolonged duration of action for morphine in very young infants. Peters et al. Morphine pharmacokinetics during venoarterial extracorporeal membrane oxygenation in neonates.
Clearance at the start of ECMO was low but increased rapidly and reached normal levels after 14 days. The only covariates affecting clearance were size and age. The distribution volume increased throughout ECMO, to a volume 2. This finding suggests that serum concentrations decrease during the first 10 days and that dose adjustments should be performed. Clinicians should also be aware that serum morphine concentrations may decrease over time in children receiving morphine infusion while undergoing ECMO; this is attributable to increased clearance and distribution volume.
Consequently, morphine therapy should be guided by clinical monitoring, preferably using validated comfort scales. Geiduschek el al. Morphine pharmacokinetics during continuous infusion of morphine sulfate for infants receiving extracorporeal membrane oxygenation. Crit Care Med. However, morphine concentrations were no different from baseline to 3 hours after beginning ECMO and no significant difference in the morphine concentration was observed in samples taken immediately proximal compared with distal to the membrane oxygenator throughout ECMO.
The initiation of ECMO thus does not lead to a significant decrease in the serum morphine concentration and there is no uptake of morphine into the membrane oxygenator of the ECMO circuit. Morphine clearance for infants receiving ECMO is variable. Dagan et al. Effects of extracorporeal membrane oxygenation on morphine pharmacokinetics in infants. The reported pharmacokinetic parameters are displayed in Table 2.
Morphine clearance rates doubled and serum concentrations were halved after ECMO was discontinued; consequently, higher doses of morphine were required to maintain adequate sedation.
The acute decrease in the serum concentrations of morphine after cessation of ECMO were probably caused by the enhanced clearance of the drug. Developmental pharmacokinetics of morphine and its metabolites in neonates, infants and young children.
Population parameter estimates for a one-compartment, first-order elimination model were standardized to a 70 kg body weight and are displayed in Table 2. The clearance of the morphine metabolites increased with age in parallel with glomerular filtration rate maturation. In another investigation, Barrett et al. Morphine kinetics after diamorphine infusion in premature neonates.
There was a direct relationship between the gestational age of the patients and the clearance and half-life of morphine, but no relationship was found between gestational age and distribution volume.
These results suggest that the currently used dosing regimen for diamorphine achieves a safe effective morphine concentration in the premature newborn but that the loading dose could be modified to achieve a more rapid onset of analgesia.
Mikkelsen et al. Morphine pharmacokinetics in premature and mature newborn infants. Acta Paediatr. Twelve of the infants received mechanical ventilation.
The median half-life in the preterm group was 9. No significant difference was found between term and preterm in terms of distribution volume or plasma clearance. The terminal half-life decreased progressively with increasing gestational age. No correlation was found between clearance and gestational age.
Finally, a larger inter-individual variation in morphine plasma concentration was observed in term infants. Farrington et al. Continuous intravenous morphine infusion in postoperative newborn infants. Am J Perinatol. Thumel et al. Dosing and optimization of dosage regimens. McGraw Hill. New York, Pp In vivo observations of morphine, paracetamol acetaminophen , and propofol disposition throughout childhood confirm the overall low glucuronidation activity in neonates observed in in vitro studies.
Compared with data related to phase 1 isoenzyme activity, data on the isoenzyme-specific phenotypic activity of uridine diphosphate glucuronosyltransferase and its covariates in neonates are limited. The present review endeavored to summarize the state of the art concerning this facet of neonatology. Stimulation of the central nervous system has been the focus of other recent reviews 36 Current pediatr reports.
As observed in Table 1 , nine of the selected articles reported on metabolic aspects of morphine processing in neonates 8 8. The most important information to be gathered from these papers is as follows: a sulfation is a minor component of morphine transformation 8 8.
The metabolism of morphine occurs not only in the liver, but may also take place in the brain and the kidneys. The glucuronides are mainly eliminated via bile and urine. Glucuronides as a rule are considered as highly polar metabolites unable to cross the blood-brain barrier. Although morphine glucuronidation has been demonstrated in human brain tissue, the capacity is very low compared to that of the liver, indicating that the M3G and M6G concentrations observed in the cerebrospinal fluid CSF after systemic administration reflect hepatic metabolism of morphine and that the morphine glucuronides, despite their high polarity, can penetrate into the brain.
Like morphine, M6G has been shown to be relatively more selective for mu-receptors than for delta- and kappa-receptors while M3G does not appear to compete for opioid receptor binding. Pain Physician. Insidious intoxication after morphine treatment in renal failure: delayed onset of morphineglucuronide action.
Retrospective study of the use of hydromorphone in palliative care patients with normal and abnormal urea and creatinine. Palliat Med. Pharmacokinetics of oral immediate-release hydromorphone Dilaudid IR in subjects with renal impairment. Proc West Pharmacol Soc. The pharmacokinetics of oxycodone in uremic patients undergoing renal transplantation. J Clin Anesthesia. Johnson SJ. Opioid safety in patients with renal or hepatic dysfunction. Pain Treatment Topics. June Accessed June 13, The pharmacokinetics and metabolism of oxycodone after intramuscular and oral administration to healthy subjects.
Br J Clin Pharmacol. Oxycodone accumulation in a hemodialysis patient. South Med J. Personalized therapy in pain management: where do we stand? Pharmacokinetics and pharmacodynamics of codeine in end-stage renal disease. Clin Pharmacol Ther. Respiratory arrest precipitated by codeine in a child with chronic renal failure. Clin Pediatrics. Successful treatment of norme-peridine neurotoxicity by hemodialysis. Koehntop D, Rodman J. Fentanyl pharmacokinetics in patients undergoing renal transplantation.
Methadone use in patients with chronic renal disease. Drug Alcohol Depend. Biopharm Drug Dispos. Br J Anaesth. Featured Issue Featured Supplements. US Pharm. Hepatic Impairment Absorption: Patients with liver cirrhosis often develop gastritis, portal hypertensive gastropathy, or ulcers of the gastrointestinal GI tract. Renal Impairment Three mechanisms influencing renal excretion of opioids exist: glomerular filtration, tubular secretion, and tubular reabsorption.
Pharmacologic Approach in Renal Impairment and Dialysis Morphine: Morphine, which was invented in , is among the oldest and most studied drugs compared to other opioid analgesics.
To comment on this article, contact rdavidson uspharmacist. Related CE. View More CE. Related Content. Take Quiz.
0コメント