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Expert Opinion on Drug Metabolism & Toxicology Volume 11, 2015 - Issue 12
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Reviews

Pharmacokinetic considerations in the use of antivirals in neonates

Elena Yu EnioutinaDivision of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, 295 Chipeta Way, Salt Lake City, UT84108, USA;Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, Salt Lake City, UT84112, USA
,
Jonathan E ConstanceDivision of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, 295 Chipeta Way, Salt Lake City, UT84108, USA
,
Chris StockmannDivision of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, 295 Chipeta Way, Salt Lake City, UT84108, USA
,
Matthew W LinakisDivision of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, 295 Chipeta Way, Salt Lake City, UT84108, USA
,
Tian YuDivision of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, 295 Chipeta Way, Salt Lake City, UT84108, USA
,
Joseph E RowerDivision of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, 295 Chipeta Way, Salt Lake City, UT84108, USA
,
Alfred H BalchDivision of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, 295 Chipeta Way, Salt Lake City, UT84108, USA
&
Catherine M SherwinDivision of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, 295 Chipeta Way, Salt Lake City, UT84108, USACorrespondence[email protected]
 show all
Pages 1861-1878 | Published online: 04 Nov 2015

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• Acyclovir use in neonates has been associated with an increased risk of neutropenia.

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• For most healthy term neonates VZV infection will follow typical disease progression. For some neonates, the infection can rapidly progress and become life-threatening, disseminating to the lungs, liver, and CNS.

•• Review described describes pharmacological aspects including pharmacokinetics of antiviral drugs used for treatment of HSV, VZV and CMV infections in neonates.

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•• One compartment model describing PK of IV acyclovir in preterm and term neonates found that PMA and weight significantly correlated with acyclovir clearance. Incorporating PMA-based dosing may improve pharmacodynamic target achievement for neonate.

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• Primary study supporting dosing of ZDV in infants.

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• Summary of 43TC pharmacokinetic.

•• Compiles much of the known information on dosing of NRTI and the associated clinical concerns.

•• Seminal paper describing tenofovir pharmacokinetics and dosing suggestions for pregnant women and newborns.

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• Describes ZDV-TP concentrations in newborns.

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• Emtricitabine-TP concentrations in newborns.

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•• Nelfinavir exhibited large interindividual variability in systemic exposure and failed to meet the exposure targets in 46% of infants who received median (range) doses of 58.8 (48. 4 –79.0) mg/kg.

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•• This research exemplified the utility of PBPK models in predicting oseltamivir pharmacokinetics in the very young (neonates).

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•• This study provided evidence for the US Food and Drug Administration’s approval (2012) of oseltamivir treatment (3 mg/kg, twice daily for 5 days) for infants with influenza aged 2 weeks through <12 months.

•• Article describes pharmacokinetics of oseltamivir for prophylaxis of influenza infection in neonates.

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