Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant

Aranda, J. V.; Varvarigou, Anastasia; Beharry, Kay D.; Bansal, Ranju; Bardin, Claudette; Modanlou, Houchang D.; Papageorgiou, Apostolos; Chemtob, Sylvain

doi:10.1111/j.1651-2227.1997.tb08892.x

Cited by 117 publications

(89 citation statements)

References 23 publications

(21 reference statements)

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“…ibuprofen lysine in preterm infants is generally over 30 h, much longer than that in adults. 21 Whether any adverse effect of ibuprofen on platelets would correspond with plasma half-life is unclear. To cover a wide range of possibilities, we obtained measurements at intervals ranging from 2 to 24 h after the first i.v.…”

Section: Discussionmentioning

confidence: 99%

Ibuprofen lysine administration to neonates with a patent ductus arteriosus: effect on platelet plug formation assessed by in vivo and in vitro measurements

et al. 2008

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Objective: Ibuprofen might have advantages over indomethacin, when used to effectuate closure of a neonate's patent ductus arteriosus (PDA). Several previous studies indicate that platelet plug formation is impaired after administration of indomethacin, but it is not clear whether a similar impairment occurs following ibuprofen dosing.Study Design: We performed template bleeding times and PFA-100 tests (platelet function analyzer) on 20 neonates who had a PDA, before and again at various preset intervals following ibuprofen dosing.Result: Patients ranged from 23 to 40 weeks gestation and weighed 511 to 2566 g. Their first dose of ibuprofen was administered at 72 h (18 to 363 h) after birth (median, range). None of the subjects had clinical bleeding problems noted during the days they received ibuprofen dosing. The template bleeding times before dosing ranged from 135 to 450 s. Repeat tests were performed in groups of four, at 2 h, 4 to 6 h, 12 to 18 h, 24 h after the first dose, and at 2 h after the third dose of ibuprofen. No changes in bleeding times were detected. (P ¼ 0.299) A PFA-100 time was performed on all 20 patients before and again after the ibuprofen administration. However, 3 of the 40 tests were unsuccessful, because of microclots in the blood sample (n ¼ 1) or failure of the analyzer for an unspecified reason (n ¼ 2). Before the dosing the PFA-100 time ranged from 52 to 300 s. A paired t-test showed a slight but statistically significant lengthening in PFA-100 time after the ibuprofen administration (P ¼ 0.019). The correlation between the bleeding time and the PFA-100 was poor (R 2 ¼ 0.212, P ¼ 0.576). Conclusion:On the basis of our present studies, we speculate that ibuprofen lysine administration to neonates with a PDA, when used according to the manufacturer's recommendations, has little adverse effect on platelet plug formation. This information might be a factor to consider when deciding whether to select indomethacin or ibuprofen for PDA closure.

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Section: Discussionmentioning

confidence: 99%

Ibuprofen lysine administration to neonates with a patent ductus arteriosus: effect on platelet plug formation assessed by in vivo and in vitro measurements

et al. 2008

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“…The levels of IBU in serum from this recommended dose is from 116 to 180 mg l À1 . 10,19 In this study, we describe the effect of higher IBU L-lysinate plasma concentration (200 and 285 mg l À1 ) on bilirubin-albumin binding in premature newborn sera and bilirubin-albumin solutions in vitro.…”

Section: Introductionmentioning

confidence: 99%

Effect of ibuprofen L-lysinate on bilirubin binding to albumin as measured by saturation index and horseradish peroxidase assays

2008

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Objective: To demonstrate, in vitro, the influence of increasing ibuprofen (IBU) concentration on bilirubin-albumin (B-A) binding. Study Design:The influence of IBU on B-A binding was measured by saturation index and horseradish peroxidase assays. B-A solutions were prepared at B:A ratios of 0.5, 1.0, 1.5 and 2.0 and bilirubin concentrations of 5 and 10 mg per 100 ml. Drug concentrations used were 142.5, 200 and 285 mg l À1 for IBU and 100 and 200 mg l À1 for acetyl salicylic acid (ASA). Similar tests were performed on premature newborn sera with bilirubin concentrations of 5 to 10 mg per 100 ml.Result: By the saturation index test, significant displacement of bilirubin from albumin with IBU was demonstrated only on B-A solution with high B:A ratio of 2.0 and IBU concentration of 285 mg l À1 and was less as compared to ASA. No displacement was observed in the sera of jaundiced neonates. By the horseradish peroxidase assay using B-A solutions, free bilirubin was significantly increased at (1) increasing concentrations of bilirubin in solution and (2) increasing B:A ratios in a solution containing 5 mg per 100 ml of bilirubin. In the sera of jaundiced neonates, significantly higher free bilirubin concentrations were observed when IBU was added to serum with bilirubin concentration of 10 mg per 100 ml as compared to 5 mg per 100 ml (0.062±0.004 versus 0.026 ± 0.005, P<0.001 by Student's t-test).Conclusion: Displacement of bilirubin was demonstrated only at high IBU concentration and high B:A ratio. However, free bilirubin levels were not shown to increase with increasing IBU concentration.

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“…NSAIDs have been used extensively for patent ductus arteriosus closure 131 and intraventricular hemorrhage prevention in preterm neonates, and they have defined pharmacokinetic/pharmacodynamic profiles. [132][133][134][135] However, the analgesic effects of NSAIDs have not been documented in preterm neonates, and the adverse effects of prolonged NSAID therapy can potentially lead to circulatory, renal, hepatic, gastrointestinal, and hematologic complications. 134 These potential complications may be especially problematic in neonates who are exposed to prolonged stress in the NICU and those who experience rapid changes in maturation of renal function.…”

Section: Procedural Painmentioning

confidence: 99%

Summary Proceedings From the Neonatal Pain-Control Group

et al. 2006

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Recent advances in neurobiology and clinical medicine have established that the fetus and newborn may experience acute, established, and chronic pain. They respond to such noxious stimuli by a series of complex biochemical, physiologic, and behavioral alterations. Studies have concluded that controlling pain experience is beneficial with respect to short-term and perhaps long-term outcomes. Yet, pain-control measures are adopted infrequently because of unresolved scientific issues and lack of appreciation for the need for control of pain and its long-term sequelae during the critical phases of neurologic maturation in the preterm and term newborn. The neonatal pain-control group, as part of the Newborn Drug Development Initiative (NDDI) Workshop I, addressed these concerns. The specific issues addressed were (1) management of pain associated with invasive procedures, (2) provision of sedation and analgesia during mechanical ventilation, and (3) mitigation of pain and stress responses during and after surgery in the newborn infant. The cross-cutting themes addressed within each category included (1) clinical-trial designs, (2) drug prioritization, (3) ethical constraints, (4) gaps in our knowledge, and (5) future research needs. This article provides a summary of the discussions and deliberations. Full-length articles on procedural pain, sedation and analgesia for ventilated infants, perioperative pain, and study designs for neonatal pain research were published in Clinical Therapeutics (June 2005).www.pediatrics.org/cgi

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Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant

Cited by 117 publications

References 23 publications

Ibuprofen lysine administration to neonates with a patent ductus arteriosus: effect on platelet plug formation assessed by in vivo and in vitro measurements

Ibuprofen lysine administration to neonates with a patent ductus arteriosus: effect on platelet plug formation assessed by in vivo and in vitro measurements

Effect of ibuprofen L-lysinate on bilirubin binding to albumin as measured by saturation index and horseradish peroxidase assays

Summary Proceedings From the Neonatal Pain-Control Group

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