Abstract:
:Among pediatric patients, preterm neonates and newborns are the most vulnerable subpopulation. Rapid developmental changes of physiological factors affecting the pharmacokinetics of drug substances in newborns require extreme care in dose and dose regimen decisions. These decisions could be supported by in silico methods such as physiologically-based pharmacokinetic (PBPK) modeling. In a comprehensive literature search, the physiological information of preterm neonates that is required to establish a PBPK model has been summarized and implemented into the database of a generic PBPK software. Physiological parameters include the organ weights and blood flow rates, tissue composition, as well as ontogeny information about metabolic and elimination processes in the liver and kidney. The aim of this work is to evaluate the model's accuracy in predicting the pharmacokinetics following intravenous administration of two model drugs with distinct physicochemical properties and elimination pathways based on earlier reported in vivo data. To this end, PBPK models of amikacin and paracetamol have been set up to predict their plasma levels in preterm neonates. Predicted plasma concentration-time profiles were compared to experimentally obtained in vivo data. For both drugs, plasma concentration time profiles following single and multiple dosing were appropriately predicted for a large range gestational and postnatal ages. In summary, PBPK simulations in preterm neonates appear feasible and might become a useful tool in the future to support dosing decisions in this special patient population.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Claassen K,Thelen K,Coboeken K,Gaub T,Lippert J,Allegaert K,Willmann Sdoi
10.2174/1381612821666150901110533subject
Has Abstractpub_date
2015-01-01 00:00:00pages
5688-98issue
39eissn
1381-6128issn
1873-4286pii
CPD-EPUB-70072journal_volume
21pub_type
杂志文章,评审abstract::Nucleoside reverse transcriptase inhibitors (NRTIs) are components of most current antiretroviral (ARV) regimens. Side effects arising from mitochondrial toxicity (MtT) induced by these drugs is a common reason why patients treated with NRTI change or discontinue therapy. These toxicities can be difficult to reverse, ...
journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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abstract::Peroxynitrite, the product of the reaction between nitric oxide and superoxide, is spontaneouly formed within most mammalian cells under physiological conditions. Initial work addressing the pathophysiology of peroxynitrite afforded the generally accepted notion that this compound would be the long-term neurotoxic nit...
journal_title:Current pharmaceutical design
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abstract::The use of systematic approach for the analysis of mechanism of action of drugs at different levels of biological organization of organisms is an important task in experimental and clinical pharmacology for drug designing and increasing the efficacy and safety of drugs. The analysis of published data on pharmacologica...
journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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更新日期:2003-01-01 00:00:00
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journal_title:Current pharmaceutical design
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abstract::The brain is a complex, regulated organ with a highly controlled access mechanism: The Blood-Brain Barrier (BBB). The selectivity of this barrier is a double-edged sword, being both its greatest strength and weakness. This weakness is evident when trying to target therapeutics against diseases within the brain. Diseas...
journal_title:Current pharmaceutical design
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更新日期:2018-01-01 00:00:00
abstract::Cancer and tumor have been major reasons for numerous deaths in this century across the world. Many strategies have been designed to treat, diagnose, or prevent cancer. The success of chemotherapy largely depends on drug targeting. The advent of nanotechnology has vastly improved drug delivery for targeting and diagno...
journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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abstract::Over the past decade, Lymphocyte Function-Associated Antigen-1 (LFA-1, alphaLbeta2, CD11a/CD18) has emerged as an attractive therapeutic target for the treatment of multiple inflammatory diseases. Its established role in the trafficking and activation of leukocytes coupled with the recent elucidation of the global con...
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abstract::Release of acetylcholine from parasympathetic nerves in the airways activates postjunctional muscarinic receptors present on smooth muscle, submucosal glands and blood vessels. This triggers bronchoconstriction, muscle hypertrophy, mucus secretion, and vasodilatation, respectively. The release of acetylcholine from pa...
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abstract::From a complications standpoint, diabetes mellitus is a disease of the vasculature. Diabetics face a considerably higher risk of developing cardiovascular and cerebrovascular diseases. Both large and small blood vessels are susceptible to alterations from diabetes. Endothelial cell dysfunction associated with small ve...
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