Development of a Physiologically-Based Pharmacokinetic Model for Preterm Neonates: Evaluation with In Vivo Data.

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 Des

authors

Claassen K,Thelen K,Coboeken K,Gaub T,Lippert J,Allegaert K,Willmann S

doi

10.2174/1381612821666150901110533

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

5688-98

issue

39

eissn

1381-6128

issn

1873-4286

pii

CPD-EPUB-70072

journal_volume

21

pub_type

杂志文章,评审
  • Impact of mitochondrial toxicity of HIV-1 antiretroviral drugs on lipodystrophy and metabolic dysregulation.

    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

    pub_type: 杂志文章,评审

    doi:10.2174/138161210793563482

    authors: Feeney ER,Mallon PW

    更新日期:2010-10-01 00:00:00

  • Harnessing anesthesia and brain imaging for the study of human consciousness.

    abstract::Philosophers have been trying to solve the mind-body problem for hundreds of years. Consciousness is the core of this problem: How do subjective conscious sensations, perceptions, feelings, and thoughts arise out of objective physical brain activities? How is this subjective conscious world in causal interaction with ...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:

    authors: Långsjo JW,Revonsuo A,Scheinin H

    更新日期:2014-01-01 00:00:00

  • Immunological properties of donkey's milk: its potential use in the prevention of atherosclerosis.

    abstract::Donkey's milk is the best substitute of human milk for its content in lactose, proteins, minerals, and omega-3 fatty acids. Here, we have evaluated the effects of colostrum and milk from donkeys (Martina Franca breed) on the function of human peripheral blood mononuclear cells (PBMCs) at different intervals from lacta...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章

    doi:10.2174/138161207783018590

    authors: Tafaro A,Magrone T,Jirillo F,Martemucci G,D'Alessandro AG,Amati L,Jirillo E

    更新日期:2007-01-01 00:00:00

  • Regulatory T cells: major players in the tumor microenvironment.

    abstract::Over the last years a number of reports have described elevated numbers of regulatory T (Treg) cells inside of tumors, in close proximity of the tumor, draining lymph nodes and also in peripheral blood of patients with solid tumors and hematologic malignancies. There is increasing evidence that Treg cells can migrate ...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161209788453211

    authors: Beyer M,Schultze JL

    更新日期:2009-01-01 00:00:00

  • In vitro modeling of the blood-brain barrier: simplicity versus complexity.

    abstract::Proper understanding of blood-brain barrier (BBB) regulation is crucial to reduce/prevent its disruption during injury. Since high brain complexity makes interpretation of in vivo data challenging BBB studies are frequently performed using simplified in vitro models. Although such models represent an important and fre...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161211797440159

    authors: Ogunshola OO

    更新日期:2011-01-01 00:00:00

  • Chemical Senses in Cancer Patients.

    abstract:BACKGROUND:Cancer and its treatment therapies, such as chemotherapy and radiotherapy, have negative effects on taste and smell functions. It is easy to explain smell and taste dysfunctions when a cancer involves the peripheric end organs or neurologic pathways of smell and taste. However, it is difficult to understand ...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612822666160216150956

    authors: Altundag A,Cayonu M

    更新日期:2016-01-01 00:00:00

  • Nanoscale Delivery Systems: Actual and Potential Applications in the Natural Products Industry.

    abstract:BACKGROUND:Compounds and extracts derived from natural sources continue to stand in the spotlight of drug design owing to their versatile interaction with enzymes, receptors and metabolic pathways. Nanomedicine offers an operative tool for the efficient delivery of natural products, in terms of increased bioavailabilit...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612823666170220155540

    authors: Simona AD,Florina A,Rodica CA,Evelyne O,Maria-Corina S

    更新日期:2017-01-01 00:00:00

  • Ligand Conjugated Targeted Nanotherapeutics for Treatment of Neurological Disorders.

    abstract:BACKGROUND:Human brain is amongst the most complex organs in human body, and delivery of therapeutic agents across the brain is a tedious task. Existence of blood brain barrier (BBB) protects the brain from invasion of undesirable substances; therefore it hinders the transport of various drugs used for the treatment of...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612826666200417141600

    authors: Mittal S,Ashhar MU,Qizilbash FF,Qamar Z,Narang JK,Kumar S,Ali J,Baboota S

    更新日期:2020-01-01 00:00:00

  • Interleukin-18, from neuroinflammation to Alzheimer's disease.

    abstract::A large body of evidence on brain development and ageing has revealed that inflammatory processes profoundly affect brain functions during life span of mammalians, including humans. Activation of innate immune mechanisms leading to pro-inflammatory cytokine up-regulation is involved in devastating and disabling human ...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161210794519147

    authors: Bossù P,Ciaramella A,Salani F,Vanni D,Palladino I,Caltagirone C,Scapigliati G

    更新日期:2010-01-01 00:00:00

  • Gastroduodenal safety of cyclooxygenase-2 inhibitors.

    abstract::Cyclooxygenase-1 (COX-1) derived eicosanoids promote gastroprotective mucosal defenses and induce platelet aggregation. By sparing COX-1, COX-2 specific inhibitors provide effective anti-inflammatory and analgesic activity while substantially reducing the risk of peptic ulcer disease and GI bleeding compared to dual C...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612033454018

    authors: Scheiman JM

    更新日期:2003-01-01 00:00:00

  • Essential Oil and Ethanol Extract of Oregano (Origanum vulgare L.) from Armenian Flora as a Natural Source of Terpenes, Flavonoids and other Phytochemicals with Antiradical, Antioxidant, Metal Chelating, Tyrosinase Inhibitory and Antibacterial Activity.

    abstract:BACKGROUND:Origanum vulgare is used in Armenian cuisine as well as in folk medicine. The aim of this investigation was to determine the peculiarities of the chemical composition of Armenian flora's oregano essential oil (EO) and ethanol extract (EE) and to characterize mainly antioxidant and antibacterial properties in...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章

    doi:10.2174/1381612825666190702095612

    authors: Moghrovyan A,Sahakyan N,Babayan A,Chichoyan N,Petrosyan M,Trchounian A

    更新日期:2019-01-01 00:00:00

  • Syngonanthus nitens (Bong.) Ruhland Derivatives Loaded into a Lipid Nanoemulsion for Enhanced Antifungal Activity Against Candida parapsilosis.

    abstract:BACKGROUND:Vaginal infections caused by non-albicans species have become common in women of all age groups. The resistance of species such as Candida parapsilosis to the various antifungal agents is a risk factor attributed to these types of infections, which instigates the search for new sources of active compounds in...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章

    doi:10.2174/1381612826666200317131041

    authors: C de Lima L,A S Ramos M,Toledo LG,Rodero CF,Hilário F,Dos Santos LC,Chorilli M,Bauab TM

    更新日期:2020-01-01 00:00:00

  • Provoking neuroprotection by peroxynitrite.

    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

    pub_type: 杂志文章,评审

    doi:10.2174/1381612043452910

    authors: Bolanos JP,García-Nogales P,Almeida A

    更新日期:2004-01-01 00:00:00

  • Pharmacological Aspects of Neuro-Immune Interactions.

    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

    pub_type: 杂志文章,评审

    doi:10.2174/1381612823666170829135115

    authors: Tarasov VV,Kudryashov NV,Chubarev VN,Kalinina TS,Barreto GE,Ashraf GM,Aliev G

    更新日期:2018-01-01 00:00:00

  • Ghrelin as a potential anti-obesity target.

    abstract::In order to develop an effective pharmacological treatment for obesity, an endogenous factor that promotes a positive energy balance by increasing appetite and decreasing fat oxidation could represent the drug target scientists have been looking for. The recently discovered gastric endocrine agent ghrelin, which appea...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612033454748

    authors: Horvath TL,Castañeda T,Tang-Christensen M,Pagotto U,Tschöp MH

    更新日期:2003-01-01 00:00:00

  • Exercise as an anabolic stimulus for bone.

    abstract::Mechanical loading provides an anabolic stimulus for bone. More importantly, the mechanosensing apparatus in bone directs osteogenesis to where it is most needed for improving bone strength. The biological processes involved in bone mechanotransduction are poorly understood and further investigation of the molecular m...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612043383755

    authors: Turner CH,Robling AG

    更新日期:2004-01-01 00:00:00

  • Peptide Mediated Brain Delivery of Nano- and Submicroparticles: A Synergistic Approach.

    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

    pub_type: 杂志文章

    doi:10.2174/1381612824666171201115126

    authors: McCully M,Sanchez-Navarro M,Teixido M,Giralt E

    更新日期:2018-01-01 00:00:00

  • Lipid-based Nanocarriers for Cancer and Tumor Treatment.

    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

    pub_type: 杂志文章

    doi:10.2174/1381612826666200720235752

    authors: Ansari MT,Ramlan TA,Jamaluddin NN,Zamri N,Salfi R,Khan A,Sami F,Majeed S,Hasnain MS

    更新日期:2020-01-01 00:00:00

  • Phosphodiesterase type 5 inhibitors: molecular pharmacology and interactions with other phosphodiesterases.

    abstract::Erectile function is determined by tight regulation of relaxation or contraction of corpus cavernosal smooth muscle, which is the result of a long and complex chain of molecular events. Control of erectile function resides in signaling pathways of the central and peripheral nervous system, as well as intracellular eve...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161205774913426

    authors: Seftel AD

    更新日期:2005-01-01 00:00:00

  • P2-pyrimidinergic receptors and their ligands.

    abstract::Pyrimidine nucleotides, including UTP, UDP and UDP-glucose, are important signaling molecules which activate G protein-coupled membrane receptors of the P2Y family. Four distinct pyrimidine nucleotide-sensitive P2Y receptor subtypes have been cloned, P2Y(2), P2Y(4), P2Y(6) and P2Y(14). Pharmacological experiments indi...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612023392937

    authors: Müller CE

    更新日期:2002-01-01 00:00:00

  • Phytoestrogen-Rich Dietary Supplements in Anti-Atherosclerotic Therapy in Postmenopausal Women.

    abstract::Cardiovascular diseases remain the leading cause of morbidity and mortality among postmenopausal women in western societies. There are still no specific and highly efficient methods of preservation of women's vascular health in modern preventive medicine. For many years physicians have assumed that hormone replacement...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612822666151112150520

    authors: Sobenin IA,Myasoedova VA,Orekhov AN

    更新日期:2016-01-01 00:00:00

  • The implications of human stem cell differentiation to endothelial cell via fluid shear stress in cardiovascular regenerative medicine: a review.

    abstract::Stem cell therapy heralds a new chapter in cardiovascular regenerative medicine. Cardiovascular implants are often used in both surgery and interventional cardiology. Cardiovascular stents are utilized in percutaneous coronary interventions (PCI), and are classified as either bare metal stents (BMS) or drug-eluting st...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161210794455058

    authors: Tan A,Sumpio BE,Lee S,Seifalian AM

    更新日期:2010-01-01 00:00:00

  • Activated immune system and inflammation in healthy ageing: relevance for tryptophan and neopterin metabolism.

    abstract::Immune activation not only accompanies inflammation in various disorders including infections, autoimmune syndromes and cancer, but it also represents a characteristic feature of ageing. Immune deviations which are most widely expressed in the elderly include increased neopterin production and tryptophan breakdown. Th...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612820666140317110217

    authors: Capuron L,Geisler S,Kurz K,Leblhuber F,Sperner-Unterweger B,Fuchs D

    更新日期:2014-01-01 00:00:00

  • Oxygen, reactive oxygen species and tissue damage.

    abstract::The diatomic molecule of oxygen contains two uncoupled electrons and can therefore undergo reduction, yielding several different oxygen metabolites, which are collectively called Reactive Oxygen Species or ROS. They are invariably produced in aerobic environments through a variety of mechanisms, which include electron...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612043384664

    authors: Bergamini CM,Gambetti S,Dondi A,Cervellati C

    更新日期:2004-01-01 00:00:00

  • Role of C reactive protein (CRP) in leptin resistance.

    abstract::Increased plasma levels of both leptin and C reactive protein (CRP) have been reported in a number of conditions, including obesity, and have been linked to cardiovascular pathophysiological processes and increased cardiovascular risk; interestingly these two biomarkers appear to be able to reciprocally regulate their...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/13816128113199990016

    authors: Hribal ML,Fiorentino TV,Sesti G

    更新日期:2014-01-01 00:00:00

  • Gender Differences in Non-Obstructive Coronary Artery Disease.

    abstract::Subjects affected by ischemic heart disease with non-obstructive coronary arteries constitute a population that has received increasing attention over the past two decades. Since the first studies with coronary angiography, female patients have been reported to have non-obstructive coronary artery disease more frequen...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章

    doi:10.2174/1381612826666201012163845

    authors: Bergami M,Scarpone M,Cenko E,Varotti E,Amaduzzi PL,Manfrini O

    更新日期:2020-10-12 00:00:00

  • LFA-1 as a key regulator of immune function: approaches toward the development of LFA-1-based therapeutics.

    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...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161206777947731

    authors: Giblin PA,Lemieux RM

    更新日期:2006-01-01 00:00:00

  • Treatment of disorders characterized by reversible airway obstruction in childhood: are anti-cholinergic agents the answer?

    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...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612811209023061

    authors: Quizon A,Colin AA,Pelosi U,Rossi GA

    更新日期:2012-01-01 00:00:00

  • Importance of ABC Transporters in Drug Development.

    abstract::ATP-binding cassette (ABC) transporters are a huge family of ATP-dependent transmembrane proteins whose main function is exporting or importing substances or molecules through the cell membranes, plasma cell membrane, or inner membranes in organelles. They fulfill these functions by maintaining cell integrity, metabol...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612822666160810120359

    authors: Benadiba M,Maor Y

    更新日期:2016-01-01 00:00:00

  • Diabetes, cognitive function, and the blood-brain barrier.

    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...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161208784705441

    authors: Huber JD

    更新日期:2008-01-01 00:00:00