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A Multi-Center Evaluation of the Pharmacokinetics and Safety of Intravenous Ibuprofen in Infants 1–6 Months of Age

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Abstract

Background

Enteral ibuprofen was first approved as a prescription drug in 1974 for the US market. An intravenous (IV) ibuprofen formulation is approved for use in children older than 6 months of age, but there are limited studies specifically evaluating the pharmacokinetics and safety in children 1–6 months of age.

Aims

The primary purpose of this study was to evaluate the pharmacokinetics of IV ibuprofen in infants younger than 6 months of age. The secondary objective was to evaluate the safety of single and repeated doses of IV ibuprofen in infants younger than 6 months of age.

Methods

This was an industry-sponsored multi-center study. Institutional Review Board approval and informed parental consent were obtained prior to enrollment. Hospitalized neonates and infants younger than 6 months of age with fever or expected postoperative pain were eligible. Enrolled patients received 10 mg/kg of IV ibuprofen every 6 h, with up to four doses per day. Patients were randomized to two sparse sampling technique pharmacokinetic sample time groups. Group 1 samples were drawn at 0, 30 min, and 2 h, while group 2 samples were drawn at 0 min, 1, and 4 h after administration.

Results

A total of 24 children were enrolled in the study, with 15 male patients and 9 female patients. The median age of the cohort was 4.4 months (range 1.1–5.9 months), and the median weight was 5.9 kg (range 2.3–8.8 kg). The arithmetic mean and standard error for peak plasma ibuprofen concentration was 56.28 ± 2.77 µg/mL. Plasma levels declined rapidly with a mean elimination half-life of 1.30 h. Time to peak ibuprofen effect and concentration were similar when compared with older pediatric patients. Clearance and volume of distribution were also similar to those reported in older pediatric patients. No drug-related adverse events were reported.

Conclusions

The pharmacokinetic and short-term safety profiles of IV ibuprofen in pediatric patients 1–6 months of age are comparable to those in children older than 6 months of age.

Trial Registration

Clinicaltrials.gov Trial Registration number and date: NCT02583399—Registered July 2017.

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Author information

Authors and Affiliations

  1. Department of Anesthesiology, Perioperative and Pain Medicine, Texas Children’s Hospital, Baylor College of Medicine, 6621 Fannin Street, Houston, TX, 77030-2399, USA

    Chris D. Glover & Nihar V. Patel

  2. “Just For Kids” Critical Care Center, Norton Children’s Hospital, Louisville, KY, USA

    John W. Berkenbosch

  3. Kosair Charities Pediatric Clinical Research Unit, University of Louisville, 231 E. Chestnut St, N-97, Louisville, KY, 40202, USA

    John W. Berkenbosch

  4. Department of Pediatrics, Suzan B. Thames Chair, Pediatric Critical Care and Pediatric Cardiology, Children’s of Mississippi, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA

    Mary B. Taylor

  5. Clinical Operations, Cumberland Pharmaceuticals Inc., 1600 West End Avenue, Suite 1300, Nashville, TN, 37203, USA

    Byron Kaelin & Breanne H. Y. Gibson

  6. Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Children’s Health of Dallas, 1935 Medical District Drive, Suite D2085, Dallas, TX, 75235, USA

    John Zhong

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  1. Chris D. Glover
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Corresponding author

Correspondence to John Zhong.

Ethics declarations

Funding

This clinical trial was sponsored by Cumberland Pharmaceuticals Inc.

Conflict of interest

CDG, JWB, MBT, NVP, and JZ were investigators on this clinical trial. BK and BHYG are employees of Cumberland Pharmaceuticals Inc.

Ethics approval

All studies were conducted following approval by site Institutional Review Boards and performed in accordance with the Declaration of Helsinki.

Consent

Prior to any study-related procedures, written informed consent was obtained from the parent or legal guardian of the patient.

Author contributions

CDG, JWB, MBT, NVP, and JZ were investigators in the clinical study. BK developed study design and BHYG prepared the data. All authors contributed to drafting the manuscript, providing critical revisions, and approving the final manuscript.

Data availability

The data that support the findings of this study are available on request from the corresponding author.

Code availability

Not applicable.

Supplementary Information

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Supplementary file1 (PDF 138 KB)

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Glover, C.D., Berkenbosch, J.W., Taylor, M.B. et al. A Multi-Center Evaluation of the Pharmacokinetics and Safety of Intravenous Ibuprofen in Infants 1–6 Months of Age. Pediatr Drugs 25, 585–593 (2023). https://doi.org/10.1007/s40272-023-00576-9

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