Pharmacokinetics of Propofol after a Single Dose in Children Aged 1–3 Years with Minor Burns

Murat, I.; Billard, V.; Vernois, J; Zaouter, M.; Marsol, P.; Souron, R; Farinotti, Robert

doi:10.1097/00000542-199603000-00006

Cited by 112 publications

(78 citation statements)

References 27 publications

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“…The calculated 4MU/UGT1A9 clearance was flow-limited and showed similarities to clinical propofol clearance, which over 50% hepatically glucuronidated by UGT1A9 (Murat et al, 1996;Rowland et al, 2008). Clearance per body weight is higher in younger children than in adults.…”

Section: Miyagi Et Almentioning

confidence: 77%

Neonatal Development of Hepatic UGT1A9: Implications of Pediatric Pharmacokinetics

Miyagi

Milne²,

Coughtrie³

et al. 2012

Drug Metabolism and Disposition

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ABSTRACT:This article reports on the development of UDP-glucuronosyltransferase 1A9 (UGT1A9) in neonatal and pediatric liver. The substrate 4-methylumbelliferone (4MU) with specific inhibition by niflumic acid was used to define specific UGT1A9 activity. Subsequently, in silico pharmacokinetic (PK) and physiology-based pharmacokinetic (PBPK) modeling was used to determine UGT1A9 maturation and hepatic clearance. Modeled maximal enzyme activity was 27.9 nmol ⅐ min ؊1 ⅐ mg protein

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Section: Miyagi Et Almentioning

confidence: 77%

Neonatal Development of Hepatic UGT1A9: Implications of Pediatric Pharmacokinetics

Miyagi

Milne²,

Coughtrie³

et al. 2012

Drug Metabolism and Disposition

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“…Toddlers [19] Twelve toddlers with minor burns, who had a median bodyweight of 11.2 (8.7-18.9) kg and age of 17.8 (12-31) months, were administered 4 mg kg −1 propofol just before bathing.…”

Section: Subjects Of the Original Studiesmentioning

confidence: 99%

“…Type II models: For the type II models, the data of the seven propofol studies [17][18][19][20][21][22][23] were regrouped into five age groups as defined by the FDA Guidance for industry of 1998 [16]:…”

Section: Combined Datasets That Were Analyzedmentioning

confidence: 99%

The allometric exponent for scaling clearance varies with age: a study on seven propofol datasets ranging from preterm neonates to adults

Wang

Allegaert

Peeters

et al. 2013

Brit J Clinical Pharma

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AIMFor scaling clearance between adults and children, allometric scaling with a fixed exponent of 0.75 is often applied. In this analysis, we performed a systematic study on the allometric exponent for scaling propofol clearance between two subpopulations selected from neonates, infants, toddlers, children, adolescents and adults. METHODSSeven propofol studies were included in the analysis (neonates, infants, toddlers, children, adolescents, adults1 and adults2). In a systematic manner, two out of the six study populations were selected resulting in 15 combined datasets. In addition, the data of the seven studies were regrouped into five age groups (FDA Guidance 1998), from which four combined datasets were prepared consisting of one paediatric age group and the adult group. In each of these 19 combined datasets, the allometric scaling exponent for clearance was estimated using population pharmacokinetic modelling (NONMEM 7.2). RESULTSThe allometric exponent for propofol clearance varied between 1.11 and 2.01 in cases where the neonate dataset was included. When two paediatric datasets were analyzed, the exponent varied between 0.2 and 2.01, while it varied between 0.56 and 0.81 when the adult population and a paediatric dataset except for neonates were selected. Scaling from adults to adolescents, children, infants and neonates resulted in exponents of 0.74, 0.70, 0.60 and 1.11 respectively.

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“…This drug potentiates the effect of GABA by inducing tyrosine kinasemediated phosphorylation of the ␤ subunits of the GABAA receptor complex (68). Despite controversy (69,70), this agent is commonly used in young children (71), including neonates (72). Toxicity of propofol for specific neurons has been shown in different in vitro and in vivo models (Table 2).…”

Section: Experimental Data On the Effects Of Analgesics And Sedative mentioning

confidence: 99%

Use of Analgesic and Sedative Drugs in the NICU: Integrating Clinical Trials and Laboratory Data

et al. 2010

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Recent advances in neonatal intensive care include and are partly attributable to growing attention for comfort and pain control in the term and preterm infant requiring intensive care. Limitation of painful procedures is certainly possible, but most critically ill infants require unavoidable painful or stressful procedures such as intubation, mechanical ventilation, or catheterization. Many analgesics (opioids and nonsteroidal anti-inflammatory drugs) and sedatives (benzodiazepines and other anesthetic agents) are available but their use varies considerably among units. This review summarizes current experimental knowledge on the effects of sedative and analgesic drugs on brain development and reviews clinical evidence that speaks for or against the use of common analgesic and sedative drugs in the NICU but avoids any discussion of anesthesia during surgery. Risk/benefit ratios of intermittent boluses or continuous infusions for the commonly used sedative and analgesic agents are discussed in the light of clinical and experimental studies. The limitations of extrapolating experimental results from animals to humans must be considered while making practical recommendations based on the currently available evidence.

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Pharmacokinetics of Propofol after a Single Dose in Children Aged 1–3 Years with Minor Burns

Cited by 112 publications

References 27 publications

Neonatal Development of Hepatic UGT1A9: Implications of Pediatric Pharmacokinetics

Neonatal Development of Hepatic UGT1A9: Implications of Pediatric Pharmacokinetics

The allometric exponent for scaling clearance varies with age: a study on seven propofol datasets ranging from preterm neonates to adults

Use of Analgesic and Sedative Drugs in the NICU: Integrating Clinical Trials and Laboratory Data

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