A Compartmental Analysis for Morphine and Its Metabolites in Young Children After a Single Oral Dose

Mendizábal, Nieves Vélez de; Jiménez-Méndez, Ricardo; Cooke, Erin; Montgomery, Carolyne J.; Dawes, Joy; Rieder, Michael J.; Aleksa, Katarina; Koren, Gideon; Jacobo-Cabral, Carlos O.; González-Ramírez, Rodrigo; Castañeda‐Hernández, Gilberto; Carleton, Bruce

doi:10.1007/s40262-015-0256-4

Cited by 12 publications

(9 citation statements)

References 30 publications

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“…Recently, several morphine PK models were published to describe the concentration-time profiles of morphine and its 2 major metabolites, M3G and M6G, in adult or pediatric patients after oral administration. 27,28 However, the first-pass effect was estimated as part of the systemic clearance of morphine after oral administration. The concentration-time profile after IV administration of M3G and M6G 19,20 provided the possibility to estimate the absolute volume of distribution and clearance for these 2 metabolites.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the amount of metabolite from the first‐pass metabolism could not be separated out from the total amount of metabolite in the system circulation, which is a combination of metabolite formed from first‐pass metabolism and systematic metabolism. Recently, several morphine PK models were published to describe the concentration‐time profiles of morphine and its 2 major metabolites, M3G and M6G, in adult or pediatric patients after oral administration . However, the first‐pass effect was estimated as part of the systemic clearance of morphine after oral administration.…”

Section: Discussionmentioning

confidence: 99%

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Integrated Model to Describe Morphine Pharmacokinetics in Humans

Liu

Ivaturi

Gobburu

2019

The Journal of Clinical Pharma

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The pharmacokinetics (PK) of morphine has been extensively investigated. Though different publications have focused on the various aspects of morphine PK, none have quantitatively interpreted morphine PK across different publications. The objective of this research is to summarize the current understanding of morphine PK in humans quantitatively. In this research, a parent-metabolite compartmental PK modeling approach was used to summarize the current understanding of morphine PK in humans. Plasma concentration-time profiles and cumulative urine recovery time profiles of morphine, morphine-3-glucuronide, and morphine-6-glucuronide were digitized from the previous publications to develop the parent-metabolite PK model. The parent-metabolite PK model successfully described the plasma concentration-time profiles and cumulative urine recovery of morphine as well as its two major metabolites, morphine-3-glucuronide and morphine-6-glucuronide, after intravenous and oral administration of morphine. This research separated out the first-pass effect on morphine metabolism after oral administration. By integrating these results with two mass balance studies of morphine, a clear picture of morphine absorption and disposition is given. Though the results are mainly based on data collected from healthy volunteers or patients whose disease is not expected to impact morphine PK, the parent-metabolite model sets a framework to further evaluate morphine PK in special populations, such as pediatrics and patients with renal impairment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Integrated Model to Describe Morphine Pharmacokinetics in Humans

Liu

Ivaturi

Gobburu

2019

The Journal of Clinical Pharma

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“…Single nucleotide polymorphisms have been described for uridine 5′‐diphospho‐glucuronosyltransferase (UGT2B7), the enzyme responsible for glucuronide conjugation of morphine; however, their impact on clearance and serum morphine and metabolite concentrations is still unresolved . Serum morphine‐3‐glucuronide (M3G) and morphine‐6‐glucuronide (M6G) concentrations were measured in this study and are reported elsewhere . Morphine‐6‐glucuronide is an active metabolite but minimally contributes to central nervous opioid effects after analgesic doses of administered morphine , and only contributes to respiratory depression in children with renal failure .…”

Section: Discussionmentioning

confidence: 99%

Oral morphine dosing predictions based on single dose in healthy children undergoing surgery

Dawes

Cooke

Hannam

et al. 2016

Pediatric Anesthesia

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“…A number of studies have described the optimal dosage of morphine. Four studies included only neonates [23][24][25][26] and four studies consisted of data solely based on children [27][28][29][30] (ranging from 10 to 40 μg/kg). The use of morphine, especially in the preterm, is still a matter for debate.…”

Section: Dose Determination Of Common Analgosedative Drugsmentioning

confidence: 99%

Analgesics and Sedatives in Critically Ill Newborns and Infants: The Impact on Long‐Term Neurodevelopment

Schiller

Allegaert

Hunfeld

et al. 2018

The Journal of Clinical Pharma

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Inadequate pain and/or stress management in preterm‐ and term‐born infants has been associated with increased morbidity and even mortality. However, exposure to analgosedatives during early infancy may also be one of the risk factors for subsequent neurodevelopmental impairment, at least in animal studies. Because infants admitted to neonatal or pediatric intensive care units may receive high amounts of these drugs for prolonged periods of time and the majority of these infants nowadays survive to discharge, this is of major concern. A balanced approach that incorporates the assessment and quantification of both wanted effects as well as unwanted side effects is therefore needed. In this article, the optimal dose determination of commonly used analgosedative drugs as well as their potential long‐term effects on the developing human brain and neuropsychological functioning are reviewed.

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A Compartmental Analysis for Morphine and Its Metabolites in Young Children After a Single Oral Dose

Cited by 12 publications

References 30 publications

Integrated Model to Describe Morphine Pharmacokinetics in Humans

Integrated Model to Describe Morphine Pharmacokinetics in Humans

Oral morphine dosing predictions based on single dose in healthy children undergoing surgery

Analgesics and Sedatives in Critically Ill Newborns and Infants: The Impact on Long‐Term Neurodevelopment

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