Renal Side Effects of Non-Steroidal Anti-Inflammatory Drugs in Neonates

Allegaert, Karel; Hoon, Jan de; Debeer, Anne; Gewillig, Marc

doi:10.3390/ph3020393

Cited by 11 publications

(7 citation statements)

References 40 publications

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“…Stochastic simulations in hypothetical preterm neonates pharmacologically treated for PDA. Figure 3 shows results of stochastic simulations in representative hypothetical patients with pharmacologically treated PDA illustrating how variability in vancomycin CL is reflected in AUC 0 -24 values following vancomycin administration with our proposed dosing (Table 1) and published dosing guidelines (Table S2), with adjustments for comedication when available (3)(4)(5)(6). Remaining variability in these plots results from random interindividual variability in vancomycin CL, for which TDM remains necessary.…”

Section: Resultsmentioning

confidence: 99%

“…Comedication given to preterm neonates with a patent (symptomatic) ductus arteriosus (PDA) includes ibuprofen and indomethacin, which have been proven to effectively induce PDA constriction and closure (3). Both nonsteroidal anti-inflammatory drugs (NSAIDs) are known to have renal side effects, as they suppress the vasodilatory effects of prostaglandins leading to vasoconstrictive renal hypoperfusion, even though exact quantification is incomplete (3,4). Vancomycin clearance (CL) was shown to decrease by 16% when coadministered with ibuprofen (5), upon which it was proposed to decrease the vancomycin dosage for neonates with PDA comedicated with ibuprofen (2).…”

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confidence: 99%

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Larger Dose Reductions of Vancomycin Required in Neonates with Patent Ductus Arteriosus Receiving Indomethacin versus Ibuprofen

Cristea

Allegaert

Falcão

et al. 2019

Antimicrob Agents Chemother

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Ibuprofen and indomethacin are commonly used to induce ductus arteriosus closure in preterm neonates. Our group previously reported that ibuprofen decreased vancomycin clearance by 16%. In this study, we quantified the impact of indomethacin coadministration on vancomycin clearance by extending our vancomycin population pharmacokinetic model with a data set containing vancomycin concentrations measured in preterm neonates comedicated with indomethacin. The modeling data set includes concentration-time data of vancomycin administered alone or in combination with either ibuprofen or indomethacin collected in the neonatal intensive care units of UZ Leuven (Leuven, Belgium) and São Francisco Xavier Hospital (Lisbon, Portugal). The derived vancomycin pharmacokinetic model was subsequently used to propose dose adjustments that yield effective vancomycin exposure (i.e., area under the concentration-time curve from 0 to 24 h [AUC 0 -24 ] between 300 to 550 mg·h/liter, with a probability of Ͻ0.1 of subtherapeutic exposure) in preterm neonates with patent ductus arteriosus. We found that indomethacin coadministration reduced vancomycin clearance by 55%. Model simulations showed that the most recent vancomycin dosing regimen, which was based on an externally validated model, requires 20% and 60% decreases of the loading and maintenance doses of vancomycin, respectively, when aiming for optimized exposure in the neonatal population. By analyzing vancomycin data from preterm neonates comedicated with indomethacin, we found a substantial decrease in vancomycin clearance of 55% versus a previously reported 16% for ibuprofen. This decrease in clearance impacts vancomycin dosing, and we anticipate that other drugs eliminated by glomerular filtration are likely to be affected to a similar extent as vancomycin.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Larger Dose Reductions of Vancomycin Required in Neonates with Patent Ductus Arteriosus Receiving Indomethacin versus Ibuprofen

Cristea

Allegaert

Falcão

et al. 2019

Antimicrob Agents Chemother

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“…Indomethacin may cause acute gastropathy, and the induced overproduction of tumor necrosis factor α (TNF α ) has also been implicated in the pathogenesis of disease state [ 76 ]. Complementarily, indomethacin to a greater extent than ibuprofen causes renal dysfunctional abnormalities in preterm neonates, and unfortunately both are the drugs of choice for patent ductus arteriosus failure [ 77 ]. The immune response in urticaria provides another good example for NSAID driven side effect [ 78 ].…”

Section: Resultsmentioning

confidence: 99%

Alleviating Promotion of Inflammation and Cancer Induced by Nonsteroidal Anti-Inflammatory Drugs

Kyriakopoulos¹,

Nagl

Baliou

et al. 2017

International Journal of Inflammation

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Clinical Relevance Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) including aspirin are of intensive use nowadays. These drugs exert their activity via the metabolism of arachidonic acid (AA) by cyclooxygenase inhibition. Though beneficial for health in some instances, both unspecific and specific cyclooxygenase inhibitor activity interfere with AA metabolism producing also proinflammatory lipids that may promote cancer. Materials and Methods This review is based on available literature on clinical uses, biochemical investigations, molecular medicine, pharmacology, toxicity, and epidemiology-clinical studies on NSAIDs and other drugs that may be used accordingly, which was collected from electronic (SciFinder, Medline, Science Direct, and ACS among others) and library searches of books and journals. Results Relevant literature supports the notion that NDSAID use may also promote proinflammatory biochemical events that are also related to precancerous predisposition. Several agents are proposed that may be employed in immediate future to supplement and optimize treatment with NSAIDs. In this way serious side effects arising from promotion of inflammation and cancer, especially in chronic NSAID users and high risk groups of patients, could be avoided.

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“…ese drugs have serious side effects and a single mechanism of action, limiting their clinical use to a certain extent [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

A Network Pharmacology Approach for Exploring the Mechanisms of Panax notoginseng Saponins in Ischaemic Stroke

Wang

Chen

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Panax notoginseng saponins (PNS) have been deemed effective herb compounds for treating ischaemic stroke (IS) and improving the quality of life of IS patients. This study aimed to investigate the underlying mechanisms of PNS in the treatment of IS based on network pharmacology. Methods. PNS were identified from the Traditional Chinese Medicine System Pharmacology (TCMSP) database, and their possible targets were predicted using the PharmMapper database. IS-related targets were identified from the GeneCards database, OMIM database, and DisGeNET database. A herb-compound-target-disease network was constructed using Cytoscape, and protein-protein interaction (PPI) networks were established with STRING. GO enrichment and KEGG pathway analysis were performed using DAVID. The binding of the compounds and key targets was validated by molecular docking studies using AutoDock Vina. The neuroprotective effect of TFCJ was substantiated in terms of oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde) and the levels of IGF1/PI3K/Akt pathway proteins. Results. A total of 375 PNS targets and 5111 IS-related targets were identified. Among these targets, 241 were common to PNS, and IS network analysis showed that MAPK1, AKT1, PIK3R1, SRC, MAPK8, EGFR, IGF1, HRAS, RHOA, and HSP90AA1 are key targets of PNS against IS. Furthermore, GO and KEGG enrichment analysis indicated that PNS probably exert therapeutic effects against IS by regulating many pathways, such as the Ras, oestrogen, FoxO, prolactin, Rap1, PI3K-Akt, insulin, PPAR, and thyroid hormone signalling pathways. Molecular docking studies further corroborated the experimental results.The network pharmacology results were further verified by molecular docking and in vivo experiments. Conclusions. The ameliorative effects of PNS against IS were predicted to be associated with the regulation of the IGF1-PI3K-Akt signalling pathway. Ginsenoside Re and ginsenoside Rb1 may play an important role in the treatment of IS.

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Renal Side Effects of Non-Steroidal Anti-Inflammatory Drugs in Neonates

Cited by 11 publications

References 40 publications

Larger Dose Reductions of Vancomycin Required in Neonates with Patent Ductus Arteriosus Receiving Indomethacin versus Ibuprofen

Larger Dose Reductions of Vancomycin Required in Neonates with Patent Ductus Arteriosus Receiving Indomethacin versus Ibuprofen

Alleviating Promotion of Inflammation and Cancer Induced by Nonsteroidal Anti-Inflammatory Drugs

A Network Pharmacology Approach for Exploring the Mechanisms of Panax notoginseng Saponins in Ischaemic Stroke

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