Reversible constriction of the fetal ductus arteriosus after maternal use of topical diclofenac and methyl salicylate

Torloni, Maria Regina; Cordioli, Eduardo; Zamith, Marina Maccagnano; Hisaba, W. J.; Nardozza, Luciano Marcondes Machado; Santana, R. M.; Moron, Antônio Fernandes

doi:10.1002/uog.2647

Cited by 32 publications

(14 citation statements)

References 17 publications

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“…This is because diclofenac has a much more potent DA-constricting activity than antipyrine or salicylic acid [5]. This estimation is consistent with the clinical observation that many more cases of DA constriction are reported for diclofenac than for the other drugs [1,23,24]. We also assumed, in this model analysis, that the concentration-response relationship for constriction of the DA in humans is equivalent to that in rats.This assumption seems reasonable, because the response is mediated by prostaglandin E2 receptor [25], for which the amino acid sequence homology between rats and humans is as high as 82% [26].…”

Section: Prediction Of Human Fetal Toxicitysupporting

confidence: 76%

Prediction and evaluation of fetal toxicity induced by NSAIDs using transplacental kinetic parameters obtained from human placental perfusion studies

Shintaku

Hori

Satoh

et al. 2012

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The use of nonsteroidal anti‐inflammatory drugs (NSAIDs) in full‐term pregnant women leads to fetal or neonatal toxicity. However, the differences in fetal toxicity among NSAIDs remain to be fully investigated.• Therefore, the ability to predict fetal toxicity of NSAIDs quantitatively at full‐term pregnancy would be of clinical value.WHAT THIS STUDY ADDS• This study presents a novel approach to predict quantitatively the fetal risk of NSAIDs administered to the mother.• This study shows that the fetal risk of diclofenac is higher than that of salicylic acid and antipyrine using the novel method.• Human placental perfusion study and pharmacokinetic/pharmacodynamic analysis may provide basic data for predicting human fetal toxicity of drugs.AIM The use of nonsteroidal anti‐inflammatory drugs (NSAIDs) in full‐term pregnant women leads to fetal or neonatal toxicity, such as constriction of the ductus arteriosus (DA) and persistent pulmonary hypertension in the newborn. The aim of this study was to predict quantitatively the fetal toxicity of three NSAIDs (antipyrine, salicylic acid and diclofenac) using the transplacental pharmacokinetic parameters obtained from our previous placental perfusion studies.METHODS Human fetal plasma concentration profile after oral administration of each NSAID to the mother was estimated using the transplacental pharmacokinetic parameters and pharmacokinetic parameters in adult women. The fetal plasma concentration–response relationship for the three NSAIDs was estimated by pharmacokinetic/pharmacodynamic analysis of the results of previous studies investigating the effects of NSAIDs on the ratio of inner diameter of the DA to that of the pulmonary artery (DA/PA) in rats and the plasma concentration profiles of NSAIDs in pregnant rats.RESULTS The risk of constriction of the DA was well predicted by the model. Mean DA/PA ratio after oral administration of diclofenac to the mother was estimated to be 39.0%, whereas both of the corresponding values after oral administration of antipyrine and salicylic acid were estimated to be 5.9%. These results suggest that the fetal risk of diclofenac is higher than those of salicylic acid and antipyrine.CONCLUSIONS This study presents a novel approach to predict quantitatively the fetal risk of NSAIDs administered to the mother. Human placental perfusion study and pharmacokinetic/pharmacodynamic analysis may provide basic data for predicting human fetal toxicity of drugs.

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Section: Prediction Of Human Fetal Toxicitysupporting

confidence: 76%

Prediction and evaluation of fetal toxicity induced by NSAIDs using transplacental kinetic parameters obtained from human placental perfusion studies

Shintaku

Hori

Satoh

et al. 2012

Brit J Clinical Pharma

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“…It has also been described after maternal use of topical diclofenac in two case reports 17 18. Diclofenac is a NSAID that is widely used; it is commonly prescribed to treat various diseases and symptoms such as inflammation and mild-to-moderate pain.…”

Section: Discussionmentioning

confidence: 99%

Prenatal constriction of the ductus arteriosus following maternal diclofenac medication in the third trimester

2015

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SUMMARYWe describe a case of a 21-year-old primigravida at 36 weeks' gestation who was admitted to a local hospital because of abdominal pain. She was prescribed a total of six doses of diclofenac 50 mg over 2 days. One day later, there was difficulty registering the fetal heartbeats on cardiotocography. Ultrasound examination revealed a fetus with ascites and pathological flow over the tricuspid valve. The patient was referred to a tertiary centre for fetal medicine. Fetal echocardiography revealed, in addition to ascites and tricuspid regurgitation, a constricted ductus arteriosus, dilated right ventricle and reduced flow in the pulmonary artery. Immediate caesarean section resulted in an excellent neonatal outcome. BACKGROUND

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“…Salsalate on the other hand is a very interesting drug in the context of diabetes and has been shown to reduce CRP, FFA, and triglycerides while increasing insulin sensitivity and adiponectin levels (Koska et al, 2009; Goldfine et al, 2010). Salsalate may, however, cause gastric irritation and should be used with caution in pregnancy (Torloni et al, 2006; Chyka et al, 2007). Collectively these studies indicate the potential of using anti-inflammatory therapeutics to attenuate T2DM.…”

Section: Inflammation and Type 2 Diabetes Mellitusmentioning

confidence: 99%

Resolution of inflammation: therapeutic potential of pro-resolving lipids in type 2 diabetes mellitus and associated renal complications

Börgeson¹,

Godson²

2012

Front. Immun.

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The role of inflammation in the pathogenesis of type 2 diabetes mellitus (T2DM) and its associated complications is increasingly recognized. The resolution of inflammation is actively regulated by endogenously produced lipid mediators such as lipoxins, resolvins, protectins, and maresins. Here we review the potential role of these lipid mediators in diabetes-associated pathologies, specifically focusing on adipose inflammation and diabetic kidney disease, i.e., diabetic nephropathy (DN). DN is one of the major complications of T2DM and we propose that pro-resolving lipid mediators may have therapeutic potential in this context. Adipose inflammation is also an important component of T2DM-associated insulin resistance and altered adipokine secretion. Promoting the resolution of adipose inflammation would therefore likely be a beneficial therapeutic approach in T2DM.

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Reversible constriction of the fetal ductus arteriosus after maternal use of topical diclofenac and methyl salicylate

Cited by 32 publications

References 17 publications

Prediction and evaluation of fetal toxicity induced by NSAIDs using transplacental kinetic parameters obtained from human placental perfusion studies

Prediction and evaluation of fetal toxicity induced by NSAIDs using transplacental kinetic parameters obtained from human placental perfusion studies

Prenatal constriction of the ductus arteriosus following maternal diclofenac medication in the third trimester

Resolution of inflammation: therapeutic potential of pro-resolving lipids in type 2 diabetes mellitus and associated renal complications

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