Cerebrospinal Fluid Distribution of Ibuprofen After Intravenous Administration in Children

Kokki, Hannu; Kumpulainen, E.; Lehtonen, Marko; Laisalmi, Merja; Heikkinen, Markku; Savolainen, Jouko; Rautio, Jarkko

doi:10.1542/peds.2007-0064

Cited by 41 publications

(38 citation statements)

References 27 publications

(33 reference statements)

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“…ibuprofen affecting platelet activation and thromboxane A 2 production and local vascular effects in the affected regions of brain vessels. It is significant that ibuprofen can penetrate into the CNS so that this may contribute to the central analgesic effects including that in headache and migraine as a consequence of local accumulation of the drug (Bannwarth et al 1995;McCrory and Fitzgerald 2004;Kokki et al 2007). Several experimental studies suggest that S(?)…”

Section: Inhibition Of Prostaglandin Synthesismentioning

confidence: 99%

Ibuprofen: pharmacology, efficacy and safety

2009

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This assessment of the safety and benefits of ibuprofen can be summarized thus: (1) Ibuprofen at OTC doses has low possibilities of serious GI events, and little prospect of developing renal and associated CV events. Ibuprofen OTC does not represent a risk for developing liver injury especially the irreversible liver damage observed with paracetamol and the occasional liver reactions from aspirin. (2) The pharmacokinetic properties of ibuprofen, especially the short plasma half-life of elimination, lack of development of pathologically related metabolites (e.g. covalent modification of liver proteins by the quinine-imine metabolite of paracetamol or irreversible acetylation of biomolecules by aspirin) are support for the view that these pharmacokinetic and notably metabolic effects of ibuprofen favour its low toxic potential. (3) The multiple actions of ibuprofen in controlling inflammation combine with moderate inhibition of COX-1 and COX-2 and low residence time of the drug in the body may account for the low GI, CV and renal risks from ibuprofen, especially at OTC doses.

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Section: Inhibition Of Prostaglandin Synthesismentioning

confidence: 99%

Ibuprofen: pharmacology, efficacy and safety

2009

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“…A single pharmacokinetic study in pediatrics investigated the CSF and plasma concentrations of intravenous ibuprofen (Ibuprof von ct. Germany) in children following inguinal surgery 37. Thirty-six children, aged 3 months to 12 years (median 40 months) received a single intravenous injection of ibuprofen (10 mg/kg).…”

Section: Pharmacokineticsmentioning

confidence: 99%

Intravenous ibuprofen: the first injectable product for the treatment of pain and fever

Bookstaver¹,

Miller²,

Rudisill³

et al. 2010

JPR

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This paper reviews the current data on the use of the first approved intravenous ibuprofen product for the management of post-operative pain and fever in the United States. The management of acute and post-operative pain and fever with nonsteroidal anti-inflammatory agents (NSAIDs) is well documented. A search in Medline and International Pharmaceutical Abstracts of articles until the end of November 2009 and references of all citations were conducted. Available manufacturer data on file were also analyzed for this report. Several randomized controlled studies have demonstrated the opioid-sparing and analgesic effects of 400 and 800 mg doses of intravenous ibuprofen in a series of post-operative patient populations. Two recent studies have also noted the improvement in fever curves in critically ill and burn patients. These data, along with pharmacokinetic and pharmacologic properties, are explored in this review, which addresses the clinical utility of a parenteral NSAID in a hospitalized patient for post-operative pain management and fever reduction. Further data on intravenous ibuprofen are needed to define long-term utilization, management of acute pain, and use in special populations.

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“…12,13 Intravenous injection of 10 mg kg À1 in children is associated with good penetration of cerebrospinal fluid, with a peak concentration attained after 30-40 min. 18 The use of the oral form of ibuprofen was advocated in our study because of its affordable pricing that would make it widely available, especially in the regions with the highest incidence of HIE. The bioavailability of ibuprofen when administered orally has been assured by different studies that proved the efficacy of oral ibuprofen in the treatment of ductus arteriosus in preterm infants.…”

Section: Discussionmentioning

confidence: 96%

Ascorbic acid combined with ibuprofen in hypoxic ischemic encephalopathy: a randomized controlled trial

et al. 2009

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Objective: Free oxygen radicals and proinflammatory cytokines are important causes for brain injury in neonates with hypoxic ischemic encephalopathy (HIE). Our objectives were to test the hypothesis that a combination of antioxidants (ascorbic acid) and anti-inflammatory agents (ibuprofen) can ameliorate the brain injury in HIE and improve neurodevelopmental outcomes when given to term infants immediately after birth.Study Design: In a prospective, randomized, double-blinded controlled trial, 60 asphyxiated term infants were assigned to one of two groups, intervention and control. The intervention group (n ¼ 30) received intravenous ascorbic acid and oral ibuprofen for 3 days; and the control group (n ¼ 30) received similar volumes of a placebo. We measured a panel of cytokines at enrollment and administered the treatment drugs within 2 h after birth. Neurological evaluations and developmental screenings were performed for all survivors at 6 months of age.Result: The Intervention and Control groups did not differ in the severity of HIE at enrollment, the concentrations of IL-1b and IL-6, the incidence of mortality (37 vs 33%), the incidence of neurological abnormalities at hospital discharge (47 vs 55%) and the incidence of developmental delay at 6 months of age (32 vs 40%), respectively. None of the observed complications were related to intervention. Serum interleukin (IL)-1b and IL-6 concentrations correlated positively with the severity of HIE at birth (P<0.01), whereas only serum IL-6 correlated with neurodevelopmental outcome at 6 months (P<0.001).Conclusion: Early administration of ascorbic acid and ibuprofen did not affect outcomes in infants with perinatal asphyxia. This study does not explain whether our intervention was not effective in blocking free radicals and inflammatory cytokines, if the dosing and route of administration were inadequate, or if other mediators existed that could have a more powerful role in brain injury during hypoxia-ischemia.

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Cerebrospinal Fluid Distribution of Ibuprofen After Intravenous Administration in Children

Abstract: Ibuprofen penetrates the cerebrospinal fluid readily, with peak concentrations attained 30 to 40 minutes after intravenous injection of a 10 mg/kg dose. The plasma analgesic concentration after inguinal surgery with spinal anesthesia is 10 to 25 mg/L.

Cited by 41 publications

References 27 publications

Ibuprofen: pharmacology, efficacy and safety

Ibuprofen: pharmacology, efficacy and safety

Intravenous ibuprofen: the first injectable product for the treatment of pain and fever

Ascorbic acid combined with ibuprofen in hypoxic ischemic encephalopathy: a randomized controlled trial

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