Age-Related Morphine Kinetics in
Infants

Pokela, Marja-Leena; Olkkola, Klaus T.; Seppαlä, Timo; Koivisto, Maila

doi:10.1159/000457538

Cited by 83 publications

(42 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, rates of morphine clearance in neonates born at term are generally greater, i.e. to 2.0-20 ml/min./kg (Lynn & Slattery 1987;McRorie et al 1992;Pokela et al 1993). It also appears that clearance not only increases with gestational age but also with postnatal age.…”

Section: Morphinementioning

confidence: 93%

Neonatal Hepatic Drug Elimination

Gow

Ghabrial

Smallwood

et al. 2001

Pharmacology & Toxicology

104

View full text Add to dashboard Cite

After the transition from in utero to newborn life, the neonate becomes solely reliant upon its own drug clearance processes to metabolise xenobiotics. Whilst most studies of neonatal hepatic drug elimination have focussed upon in vitro expression and activities of drug-metabolising enzymes, the rapid physiological changes in the early neonatal period of life also need to be considered. There are dramatic changes in neonatal liver blood flow and hepatic oxygenation due to the loss of the umbilical blood supply, the increasing portal vein blood flow, and the gradual closure of the ductus venosus shunt during the first week of life. These changes which may well affect the capacity of neonatal hepatic drug metabolism. The hepatic expression of cytochromes P450 1A2, 2C, 2D6, 2E1 and 3A4 develop at different rates in the postnatal period, whilst 3A7 expression diminishes. Hepatic glucuronidation in the human neonate is relatively immature at birth, which contrasts with the considerably more mature neonatal hepatic sulfation activity. Limited in vivo studies show that the human neonate can significantly metabolise xenobiotics but clearance is considerably less compared with the older infant and adult. The neonatal population included in pharmacological studies is highly heterogeneous with respect to age, body weight, ductus venosus closure and disease processes, making it difficult to interpret data arising from human neonatal studies. Studies in the perfused foetal and neonatal sheep liver have demonstrated how the oxidative and conjugative hepatic elimination of drugs by the intact organ is significantly increased during the first week of life, highlighting that future studies will need to consider the profound physiological changes that may influence neonatal hepatic drug elimination shortly after birth.The development of clinical pharmacology has resulted in a more rational approach to drug therapy, as well as a deeper understanding of the factors capable of influencing drug disposition, and hence drug effects. Of these factors, age is of great importance. However, substantial differences in drug disposition not only exist between neonates and adults, but also among premature neonates, term neonates, infants and children.During the last two decades drug disposition in the neonatal period has been studied extensively. A major impetus for these studies seems to have been a series of incidents involving illness or death following the administration of drugs at ratios of dose/body weight innocuous in an adult (Craft et al. 1974;Gershanik et al. 1982). These studies have shown that the transition from neonate to childhood is characterised by the ontogeny of all of the processes of drug absorption, distribution, hepatic metabolism and renal excretion, with the development of hepatic drug metabolism being particularly important.The extent to which the neonatal drug-metabolising en-

show abstract

Section: Morphinementioning

confidence: 93%

Neonatal Hepatic Drug Elimination

Gow

Ghabrial

Smallwood

et al. 2001

Pharmacology & Toxicology

104

View full text Add to dashboard Cite

show abstract

“…9 Analgesics such as fentanyl and morphine when given alone are also not the answer, as even in large doses they do not completely obtund the autonomic response to noxious stimuli, but may result in prolonged respiratory depression. [10][11][12] In the case of fentanyl, rapid large boluses can also result in sudden profound chest wall rigidity, which results in an inability to ventilate. Thus, a balanced anaesthetic using sedation, analgesia, and muscle relaxation in lower doses provides optimal conditions for treatment but with reduced side effects.…”

Section: R Hartreymentioning

confidence: 99%

Anaesthesia for the laser treatment of neonates with retinopathy of prematurity

Hartrey

2007

Eye

View full text Add to dashboard Cite

“…[69,74,75,[77][78][79][80][81][82][83][84] The results of these studies are summarised in table I. Part of the differences across the studies is probably accounted for by the various gestational ages, postnatal ages, and clinical conditions studied, as well as the various designs and dose levels applied.…”

Section: 2 Pharmacokineticsmentioning

confidence: 99%

Clinical Pharmacokinetics of Sedatives in Neonates

Jacqz-Aigrain

Burtin

1996

Clinical Pharmacokinetics

View full text Add to dashboard Cite

Sedation is currently administered to neonates experiencing pain and stress during intensive care for medical diseases, as well as postoperatively. Drugs commonly used for sedation in neonates include benzodiazepines (midazolam and lorazepam), chloral hydrate and opioids (fentanyl and morphine). Sedation protocols and dosage schedules are, in most cases, adapted from those which have been developed in children and even adults. The effectiveness and safety of the sedative agents remain underevaluated, however, due to the difficulties of quantifying pain and stress in neonates, and because of the limited use of validated scoring methods by practitioners. Among the benzodiazepines, midazolam is probably the drug of choice for continuous sedation. However, its elimination is delayed in the neonatal period and hypotension may occur when given as a bolus injection or when taken with opioids. Lorazepam requires further evaluation to exclude severe neurotoxicity. Chloral hydrate is administered orally, but because of its delayed elimination and risk of accumulation, a single administration for short term sedation is recommended. Among opioids, fentanyl (which was initially administered for postoperative analgesia) is now prescribed for sedation during mechanical ventilation. Tolerance and dependence may develop rapidly, limiting its usefulness for prolonged sedation. Although extensively studied in neonates, the efficacy and safety of morphine are not clearly determined, because of the limited number of patients included in individual studies. In addition, important interindividual differences in metabolism render dosage recommendations difficult. Alfentanil and sufentanil need further investigations to define their pharmacokinetic-pharmacodynamic properties in neonates. Although the choice of drug is important, the way the drug is used and monitored is equally important. All the drugs used for the sedation of neonates have large inter- and intraindividual differences in disposition, justifying specific pharmacological knowledge and individual dosage adjustments based on clinical evaluation of the patient and the monitoring of drug concentrations.

show abstract

Age-Related Morphine Kinetics in Infants

Cited by 83 publications

References 18 publications

Neonatal Hepatic Drug Elimination

Neonatal Hepatic Drug Elimination

Anaesthesia for the laser treatment of neonates with retinopathy of prematurity

Clinical Pharmacokinetics of Sedatives in Neonates

Contact Info

Product

Resources

About