Pediatric Pharmacokinetics

Funk, Ryan S.; Brown, Jacob T.; Abdel‐Rahman, Susan M.

doi:10.1016/j.pcl.2012.07.003

Cited by 48 publications

(10 citation statements)

References 85 publications

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“…Real-time pharmacokinetic assessment was critical to our ability to enrol infants on study, as drug exposure in very young infants can be difficult to predict due to incompletely developed drug absorption, distribution, metabolism, and elimination. 30…”

Section: Discussionmentioning

confidence: 99%

Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study

Laetsch

DuBois

Mascarenhas

et al. 2018

The Lancet Oncology

465

415

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Section: Discussionmentioning

confidence: 99%

Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study

Laetsch

DuBois

Mascarenhas

et al. 2018

The Lancet Oncology

465

415

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“…Several drug transporters in the kidney, together with those in the hepatobiliary system, are responsible for the elimination of endogenous and exogenous toxins — including drugs that are given to newborns — that are modified by hepatic drug-metabolizing enzymes (for instance, by sulphation or glucuronidation) 185,224 . In developing animal organs such as the kidney and liver, the expression of drug transporters and drug-metabolizing enzymes is relatively low at birth and then increases considerably during the postnatal period and through juvenile stages 21,29,225–227 .…”

Section: Figurementioning

confidence: 99%

“…Low drug transporter expression may be a particularly important issue in premature infants 29,224 . It may be that there is some type of remote communication between the liver and kidney to ensure that the neonatal kidney can excrete potentially toxic metabolites produced by hepatic drug-metabolizing enzymes.…”

Section: Figurementioning

confidence: 99%

What do drug transporters really do?

Nigám

2014

Nat Rev Drug Discov

452

556

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Potential drug–drug interactions mediated by the ATP-binding cassette (ABC) transporter and solute carrier (SLC) transporter families are of clinical and regulatory concern. However, the endogenous functions of these drug transporters are not well understood. Discussed here is evidence for the roles of ABC and SLC transporters in the handling of diverse substrates, including metabolites, antioxidants, signalling molecules, hormones, nutrients and neurotransmitters. It is suggested that these transporters may be part of a larger system of remote communication (‘remote sensing and signalling’) between cells, organs, body fluid compartments and perhaps even separate organisms. This broader view may help to clarify disease mechanisms, drug–metabolite interactions and drug effects relevant to diabetes, chronic kidney disease, metabolic syndrome, hypertension, gout, liver disease, neuropsychiatric disorders, inflammatory syndromes and organ injury, as well as prenatal and postnatal development.

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“…The PK of tramadol is well described in adults ( Gong et al, 2014 ). However, as for many drugs, the PK of tramadol may not be simply extrapolated from the adult’s data due to ontogeny and other age-related differences ( Kearns et al, 2003 ; Funk et al, 2012 ; Lu and Rosenbaum, 2014 ; Batchelor and Marriott, 2015 ; Allegaert et al, 2017 ). Although still limited, several studies have been carried out in children of different ages to assess its PK profile ( Murthy et al, 2000 ; Payne et al, 2002 ; Allegaert et al, 2005 , 2015 ; Garrido et al, 2006 ; Saudan and Habre, 2007 ; Vandenbossche et al, 2015 ).…”

Section: Pharmacokineticsmentioning

confidence: 99%

When the Safe Alternative Is Not That Safe: Tramadol Prescribing in Children

et al. 2018

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Children represent a vulnerable population in which management of nociceptive pain is complex. Drug responses in children differ from adults due to age-related differences. Moreover, therapeutic choices are limited by the lack of indication for a number of analgesic drugs due to the challenge of conducting clinical trials in children. Furthermore the assessment of efficacy as well as tolerance may be complicated by children’s inability to communicate properly. According to the World Health Organization, weak opioids such as tramadol and codeine, may be used in addition to paracetamol and ibuprofen for moderate nociceptive pain in both children and adults. However, codeine prescription has been restricted for the last 5 years in children because of the risk of fatal overdoses linked to the variable activity of cytochrome P450 (CYP) 2D6 which bioactivates codeine. Even though tramadol has been considered a safe alternative to codeine, it is well established that tramadol pharmacodynamic opioid effects, efficacy and safety, are also largely influenced by CYP2D6 activity. For this reason, the US Food and Drug Administration recently released a boxed warning regarding the use of tramadol in children. To provide safe and effective tramadol prescription in children, a personalized approach, with dose adaptation according to CYP2D6 activity, would certainly be the safest method. We therefore recommend this approach in children requiring chronic or recurrent nociceptive pain treatment with tramadol. In case of acute inpatients nociceptive pain management, prescribing tramadol at the minimal effective dose, in a child appropriate dosage form and after clear instructions are given to the parents, remains reasonable based on current data. In all other situations, morphine should be preferred for moderate to severe nociceptive pain conditions.

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Pediatric Pharmacokinetics

Cited by 48 publications

References 85 publications

Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study

Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study

What do drug transporters really do?

When the Safe Alternative Is Not That Safe: Tramadol Prescribing in Children

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