scholarly journals CYP2C9*2 is associated with indomethacin treatment failure for patent ductus arteriosus

2019 ◽  
Vol 20 (13) ◽  
pp. 939-946
Author(s):  
Sydney R Rooney ◽  
Elaine L Shelton ◽  
Ida Aka ◽  
Christian M Shaffer ◽  
Ronald I Clyman ◽  
...  
Keyword(s):  
Patent Ductus Arteriosus ◽  
Treatment Failure ◽  
Preterm Infants ◽  
Gestational Age ◽  
Genetic Factors ◽  
Ductus Arteriosus ◽  
Preterm Neonates ◽  
Multicenter Cohort Study ◽  
Patent Ductus ◽  
Indomethacin Treatment

Aims: To identify clinical andgenetic factors associated with indomethacin treatment failure in preterm neonates with patent ductus arteriosus (PDA). Patients & Methods: This is a multicenter cohort study of 144 preterm infants (22–32 weeks gestational age) at three centers who received at least one treatment course of indomethacin for PDA. Indomethacin failure was defined as requiring subsequent surgical intervention. Results: In multivariate analysis, gestational age (AOR 0.76, 95% CI 0.60–0.96), surfactant use (AOR 9.77, 95% CI 1.15–83.26), and CYP2C9*2 (AOR 3.74; 95% CI 1.34–10.44) were each associated with indomethacin failure. Conclusion: Age, surfactant use, and CYP2C9*2 influence indomethacin treatment outcome in preterm infants with PDA. This combination of clinical and genetic factors may facilitate targeted indomethacin use for PDA.

Wide Pulse Pressure Is Not Associated with Patent Ductus Arteriosus in the First Week of Life

2019 ◽  
Vol 36 (13) ◽  
pp. 1401-1404
Author(s):  
Alona Bin-Nun ◽  
Yair Kasirer ◽  
Francis Mimouni ◽  
Irina Schorrs ◽  
Daniel Fink ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Patent Ductus Arteriosus ◽  
Preterm Infants ◽  
Study Design ◽  
Gestational Age ◽  
Pulse Pressure ◽  
Ductus Arteriosus ◽  
Preterm Neonates ◽  
Patent Ductus

Objectives Widened pulse pressure is generally associated with patent ductus arteriosus (PDA). Surprisingly, this is often not true for preterm infants during the first week of life when systolic and diastolic pressures are both reduced and pulse pressure may remain unchanged. Study Design This is a retrospective, observational review of individual blood pressure (BP) parameters preterm neonates <30 weeks' gestational age during the first week of life as correlated with ductal patency and severity. Results Sixteen preterm neonates had a closed ductus on initial echocardiogram during the first week of life; 30 had a PDA that was open but hemodynamically insignificant; and 16 were found to have a hemodynamically significant PDA. Pulse pressure showed no correlation (p = 0.266) with the degree of ductal patency, whereas diastolic BP was best correlated with ductal severity (p < 0.001). Conclusion We found that low diastolic pressures are better correlated with ductal patency and severity than is pulse pressure in preterm neonates during the first week of life.

Oral acetaminophen administration for patent ductus arteriosus (PDA) closure in preterm neonates

2021 ◽  
Vol 43 (3) ◽  
pp. 254-259
Author(s):  
Mahmood Samadi ◽  
Zahra Nabaee ◽  
Manizheh Mostafagharebaghi ◽  
Majid Mahalei ◽  
Elham Sheykhsaran ◽  
...  
Keyword(s):  
Patent Ductus Arteriosus ◽  
Gestational Age ◽  
Statistical Significance ◽  
Ductus Arteriosus ◽  
Preterm Neonates ◽  
Term Infants ◽  
Treatment Data ◽  
Kolmogorov Smirnov ◽  
Study Population ◽  
Patent Ductus

Background: Patent Ductus Arteriosus (PDA) is considered one of the most prevalent types of congenital heart disease. The closure of the ductus arteriosus physiologically occurs at the first 48-72 hours after the birth in healthy term infants. Different causes can result in the pathological opening of ductus arteriosus. This study aims to investigate the effect of oral acetaminophen on the closure of PDA in preterm neonates. Methods: The present study is a trial without control. Forty-five preterm neonates with a gestational age of <32 weeks were studied. Acetaminophen was orally administered with a dose of 10mg/kg every 6 hours for three days. Closure of ductus arteriosus was considered as the success of treatment. Data were analyzed using SPSS 15. Data were reported as )frequency-percent) and mean ± SD. To evaluate the normal distribution of data, we used a Kolmogorov-Smirnov test. Statistical significance was defined as P<0.05. Results: The study population consisted of 20 male and 25 female infants with the mean gestational age of 28.95 ± 1.66 weeks. Cesarean-born infants and vaginal-born infants consisted 17.8% and 82.2% of the study population, respectively. The proportion of PDA closure after administration of oralacetaminophen was 82.3%. Conclusion: The current study indicates that oral acetaminophen is highly effective in closing PDA. Considering its trivial side effects, it has the potency to be a convenient option for treating this condition.

Clinical Pharmacology of Ibuprofen and Indomethacin in Preterm Infants with Patent Ductus Arteriosus

2014 ◽  
Vol 10 (3) ◽  
pp. 216-237 ◽  
Author(s):  
Gian Maria Pacifici
Keyword(s):  
Patent Ductus Arteriosus ◽  
Serum Creatinine ◽  
Prostaglandin E2 ◽  
Preterm Infants ◽  
Gestational Age ◽  
Urine Output ◽  
Ductus Arteriosus ◽  
Closure Rate ◽  
Term Infants ◽  
Patent Ductus

Background: Ibuprofen and indomethacin are potent non-selective cyclo-oxygenase inhibitors and inhibit prostaglandin E2 synthesis. The patent ductus arteriosus (PDA) occurs in more than 70% of preterm infants weighing <1500 g. Prostaglandin E2 relaxes smooth muscle, tends to inhibit the closure of PDA, yields vasodilatation of the afferent renal arterioles and maintains glomerular filtration rate (GFR). Ibuprofen and indomethacin inhibiting prostaglandin E2 synthesis close PDA and reduce GFR with consequent decrease of urine output and increase of serum creatinine concentrations. Aims: The aims of this study are to give the definitive estimates of PDA closure rate following ibuprofen or indomethacin treatment and to evaluate the extent of renal side effects following the administration of these drugs to preterm infants. Other aims are to review the metabolism and the pharmacokinetics of ibuprofen and indomethacin in preterm infants with PDA. Methods: The bibliographic search was performed using PubMed and EMBASE databases as search engines, January 2013 was the cutoff point. Results: The %PDA closed by ibuprofen (n=24) and indomethacin (n=24) is 77.7±14.1 and 77.3±11.0, respectively. For ibuprofen, the gestational age of the infants included in the study ranged from 25.0 to 39.0 weeks (mean±SD=29.3±3.1 weeks). The %PDA did not correlate with the gestational age (p=0.2516). For indomethacin, the gestational age of infants included in the study ranged from 25.0 and 39.0 weeks (mean±SD=29.4±2.9 weeks). The %PDA did not correlate with the gestational age (p=0.3742). The treatment with ibuprofen reduces the urine output and increases the serum creatinine concentrations less extensively than indomethacin. The half-life (t1/2) of ibuprofen and indomethacin is lengthened and the clearance is reduced in preterm infants as compared with fullterm infants. Conclusions. Ibuprofen and indomethacin are equally effective in closing PDA. Treatment with ibuprofen decreases the risk of renal failure. Ibuprofen has the most favourable risk/benefit ratio. The rate of metabolism is reduced and t1/2 is lengthened in prematures as compared with term infants.

Novel strategy to personalise use of ibuprofen for closure of patent ductus arteriosus in preterm neonates

2021 ◽  
pp. archdischild-2020-321381
Author(s):  
Samira Samiee-Zafarghandy ◽  
Tamara van Donge ◽  
Gerhard Fusch ◽  
Marc Pfister ◽  
George Jacob ◽  
...  
Keyword(s):  
Patent Ductus Arteriosus ◽  
Gestational Age ◽  
Ductus Arteriosus ◽  
Plasma Concentrations ◽  
Preterm Neonates ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Target Exposure ◽  
Patent Ductus

ObjectiveExploration of a novel therapeutic drug monitoring (TDM) strategy to personalise use of ibuprofen for closure of patent ductus arteriosus (PDA) in preterm neonates.DesignProspective, single-centre, open-label, pharmacokinetics study in preterm neonates.SettingNeonatal intensive care unit at McMaster Children’s Hospital.PatientsNeonates with a gestational age ≤28+6 weeks treated with oral ibuprofen for closure of a PDA.MethodsPopulation pharmacokinetic parameters, concentration-time profiles and exposure metrics were obtained using pharmacometric modelling and simulation.Main outcome measureAssociation between ibuprofen plasma concentrations measured at various sampling time points on the first day of treatment and attainment of the target exposure over the first 3 days of treatment (AUC0–72h >900 mg·hour/L).ResultsTwenty-three preterm neonates (median birth weight 780 g and gestational age 25.9 weeks) were included, yielding 155 plasma ibuprofen plasma samples. Starting from 8 hours’ postdose on the first day, a strong correlation between ibuprofen concentrations and AUC0–72h was observed. At 8 hours after the first dose, an ibuprofen concentration >20.5 mg/L was associated with a 90% probability of reaching the target exposure.ConclusionWe designed a novel and practical TDM strategy and have shown that the chance of reaching the target exposure (AUC0–72h >900 mg·hour/L) can be predicted with a single sample collection on the first day of treatment. This newly acquired knowledge can be leveraged to personalise ibuprofen dosing regimens and improve the efficacy of ibuprofen use for pharmacological closure of a PDA.

Urinary aquaporin-2 excretion during ibuprofen or indomethacin treatment in preterm infants with patent ductus arteriosus

2010 ◽  
Vol 100 (1) ◽  
pp. 59-66 ◽  
Author(s):  
Yanhong Li ◽  
Marina Zelenina ◽  
Geneviève Plat-Willson ◽  
Marie-Odile Marcoux ◽  
Anita Aperia ◽  
...  
Keyword(s):  
Patent Ductus Arteriosus ◽  
Preterm Infants ◽  
Ductus Arteriosus ◽  
Aquaporin 2 ◽  
Patent Ductus ◽  
Indomethacin Treatment

scholarly journals Association of patent ductus arteriosus (PDA) with prematurity and low birth weight neonates

2019 ◽  
Vol 6 (2) ◽  
pp. 781
Author(s):  
Gh Rasool Wani ◽  
Nazir Ahmad Parray ◽  
Mohd Rafiq Lone ◽  
Nisar Ahmad Ganie ◽  
Anwar Hussain ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Patent Ductus Arteriosus ◽  
Gestational Age ◽  
Ductus Arteriosus ◽  
Preterm Neonates ◽  
Study Cohort ◽  
Care Hospital ◽  
Number Of Patients ◽  
Patent Ductus

Background: Patent ductus arteriosus (PDA) is a major morbidity encountered in preterm neonates, especially in babies less than 28 weeks gestation or 1000g. It may close spontaneously in preterm neonates; however, failure to close spontaneously in preterm neonates results in significant mortality and morbidity in them.Methods: This prospective study was conducted in a tertiary care hospital in north India over a period of one year. The study cohort consisted of preterm, newborn babies admitted in the hospital with gestational age less than 37weeks and birth weight <2500g.Results: In this study total number of patients admitted during the study were 2930. Out of these preterm low birth weight neonates were 432. Among preterm low birth weight neonates admitted, 132 neonates were excluded as per exclusion criteria. Patent ductus arteriosus was detected in 56 among the 300 neonates giving an overall incidence of patent ductus arteriosus 18.6%, the incidence of patent ductus arteriosus was 56.2% for neonates weighing less than 1000gm, 24.7% for neonates weighing between 1000-1499g, 11.6% for neonates weighing between 1500-1999g and 5.6% for the neonates weighing between 2000-2499g.Conclusions: Thus, incidence of patent ductus arteriosus was inversely proportional to gestational age and birth. Data also suggest that immaturity is the major determinant of the persistent patency of ductus arteriosus.

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