Paracetamol and metabolite pharmacokinetics in infants

Marel, C. D. van der; Anderson, Brian J.; Lingen, Richard A. van; Holford, Nicholas H. G.; Pluim, M. A. L.; Jansman, Frank G A; Anker, John N. van den; Tibboel, Dick

doi:10.1007/s00228-003-0608-0

Cited by 76 publications

(54 citation statements)

References 36 publications

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“…72 Despite reduced clearance of acetaminophen, 79 hepatotoxicity is less common in neonates than in older infants, in part because of low levels of certain cytochrome P-450 enzymes, which convert acetaminophen into toxic metabolites. 80 Acetaminophen is available for both oral and intravenous administration.…”

Section: Pain Medicationsmentioning

confidence: 99%

The Transfer of Drugs and Therapeutics Into Human Breast Milk: An Update on Selected Topics

Sachs¹

2013

Pediatrics

469

198

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Many mothers are inappropriately advised to discontinue breastfeeding or avoid taking essential medications because of fears of adverse effects on their infants. This cautious approach may be unnecessary in many cases, because only a small proportion of medications are contraindicated in breastfeeding mothers or associated with adverse effects on their infants. Information to inform physicians about the extent of excretion for a particular drug into human milk is needed but may not be available. Previous statements on this topic from the American Academy of Pediatrics provided physicians with data concerning the known excretion of specific medications into breast milk. More current and comprehensive information is now available on the Internet, as well as an application for mobile devices, at LactMed (http://toxnet.nlm.nih.gov). Therefore, with the exception of radioactive compounds requiring temporary cessation of breastfeeding, the reader will be referred to LactMed to obtain the most current data on an individual medication. This report discusses several topics of interest surrounding lactation, such as the use of psychotropic therapies, drugs to treat substance abuse, narcotics, galactagogues, and herbal products, as well as immunization of breastfeeding women. A discussion regarding the global implications of maternal medications and lactation in the developing world is beyond the scope of this report. The World Health Organization offers several programs and resources that address the importance of breastfeeding (see http://www.who.int/topics/breastfeeding/en/).

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Section: Pain Medicationsmentioning

confidence: 99%

The Transfer of Drugs and Therapeutics Into Human Breast Milk: An Update on Selected Topics

Sachs¹

2013

Pediatrics

469

198

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“…These include physiological characteristics of organs, tissues, and blood flows as described by Johnson et al (2006) (Table 1 2006), the fraction of vascular and interstitial space, changes in total body water and adipose tissue content, plasma protein concentration especially of albumin and alpha glycoprotein, and renal and hepatic elimination. There are numerous reports about developmental changes in metabolizing enzymes from birth to adolescence (van der Marel et al 2003;Bouwmeester et al 2004; see also Table 2). Nearly each CYP450 isoform shows a different pattern of maturation, and might influence the drug clearance with respect to specific age Study Design and Simulation Approachgroups.…”

Section: Physiology-based Pharmacokinetic Modeling In Childrenmentioning

confidence: 97%

Study Design and Simulation Approach

Läer

2011

Pediatric Clinical Pharmacology

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Modeling and simulation techniques are a mainstay of clinical drug development and are particularly useful to support clinical trials in children. If a pediatrician wants to use these tools most efficiently, a basic understanding of the principles and methods of classical and novel techniques of modeling and simulation is essential. Key elements comprise the definition and description of terms like deterministic simulation, Monte Carlo simulation, classical "top down" or novel "bottom up" approach, as well as the term "virtual world simulation." The illustrated examples in this chapter from pediatric clinical trials will help to understand and demonstrate these key elements. The importance of the understanding of developmental physiology and pharmacokinetics will become visible when explaining novel "bottom up" approaches like physiologically based pharmacokinetic simulations which also bridge to current research tools from other areas such as systems biology using mathematical models to describe biological systems.

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“…8 Miller et al (1976) Single, oral Children, 3-9 years 0.75 Van der Marel et al (2003) Multiple, enteral Infants; mean, 11 months 0.69 Levy et al (1975) Single, oral Term neonates 0.27 Allegaert et al (2005) Multiple, intravenous Term neonates 0.33…”

Section: Referencesmentioning

confidence: 99%

“…Following single dose administration, a maturational increase in urinary molar G/S ratio is observed (Levy et al, 1975;Miller et al, 1976;Hendrix-Treacy et al, 1986). Although much more limited in number, observations on the urinary G/S ratio during repeated acetaminophen administration in neonates, infants, and adults more recently also became available (Hendrix-Treacy et al, 1986;Van der Marel et al, 2003;Allegaert et al, 2005) (Table 1).…”

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confidence: 99%

“…Repeated administration remained a significant contributor of urinary excretion of APAP-G to overall APAP excretion after correction for postnatal and postconception age in a multiple regression model. Van der Marel et al (2003) described acetaminophen disposition in 47 infants with a mean age of 11 months based on urine and blood samples collected following major craniofacial surgery. Acetaminophen was repeatedly administered either by oral or rectal route.…”

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confidence: 99%

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