{
  "abstract": "Background/Aim: L-Glutamine (L-Gln) has been approved for the treatment of sickle cell disease (SCD) since 2017. Clinical and pharmacological data in pediatric patients remain limited. This review summarizes studies of L-Gln use in SCD including pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy in pediatrics, alongside in-vitro and pre-clinical data elucidating primary and supplemental mechanisms of action (MOA). Pharmacoeconomics (PE) is addressed briefly.\n\nMaterials and Methods: Literature search included keywords of SCD, L-Gln, and pediatrics – targeting papers with PK, PD, PE, clinical and preclinical studies. Thirty-two articles meeting the selection criteria were included for descriptive and analytical review.\n\nResults: Two mouse studies were identified. The remaining articles included translational, Phase-2 and Phase-3 trials and studies containing pharmacological data. Pharmacokinetics showed serum L-Gln levels to peak at 800-1000 µM within 1 h after oral intake of clinically relevant doses. Thereafter, approximately 500-600 µM levels were shown to last 4-8 h post-dose. Pharmacodynamic data suggest that antioxidant effects may represent an important mechanism of action mainly via increased NADH, but additional contributors may include increased glutathione, decreased cell adhesion, and up-regulated autophagy of peripheral blood mononuclear cells. Five papers compared L-Gln with other SCD-modifying therapies. Indirect comparisons suggest that L-Gln, hydroxyurea, and crizanlizumab can each reduce vaso-occlusive events with significant decrease of pain crises and hospitalizations. However, direct comparative efficacy cannot be established in the absence of head-to-head trials. Overall safety profile was also comparable; however L-Gln may cause more gastrointestinal (GI) side effects such as constipation and abdominal pain. Annual cost of L-Gln is lower than crizanlizumab, however insurance denials and high co-pays were reported as barriers to initiating the therapy.\n\nConclusion: Oral L-Gln is an effective SCD-modifying therapy for patients with sickle cell disease 5 years and older. Gastrointestinal adverse effects, including abdominal pain and constipation, are reported. PK supports twice daily regimen, and PD suggests that anti-oxidative effect is the dominant MOA. Cost reductions may result in wider use of L-Gln.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Pediatric Hematology-Oncology, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, U.S.A.",
    "The Lundquist Institute for Biomedical Innovation, Torrance, CA, U.S.A."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "EDUARD H. PANOSYAN"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fkgr4hvn4303r.bib",
  "cited_by": 0,
  "doi": "10.21873/invivo.14475",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13723952/",
  "id": "fkgr4hvn4303r",
  "issns": [
    "0258-851X",
    "1791-7549"
  ],
  "landing_url": "https://doi.org/10.21873/invivo.14475",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review Article"
    ],
    [
      "openalex",
      "2716|Hemoglobinopathies and Related Disorders"
    ]
  ],
  "openalex": "W7224662648",
  "pdf_url": "https://iv.iiarjournals.org/content/invivo/40/6/3253.full.pdf",
  "pmcid": "PMC13723952",
  "pmid": "42957242",
  "published": "2026-10-29",
  "publisher": "International Institute of Anticancer Research",
  "ris": "https://research.draconitic.com/paper/fkgr4hvn4303r.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:22:29Z",
      "native_id": "PMC13723952",
      "source": "pmc",
      "url": "https://doi.org/10.21873/invivo.14475"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2716|Hemoglobinopathies and Related Disorders",
      "subfield": "human-genetics"
    }
  ],
  "title": "L-Glutamine for Pediatric Sickle Cell Disease: Pharmacology, Mechanism of Action, Safety and Efficacy",
  "title_text": "L-Glutamine for Pediatric Sickle Cell Disease: Pharmacology, Mechanism of Action, Safety and Efficacy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:40Z",
  "url": "https://research.draconitic.com/paper/fkgr4hvn4303r",
  "venue": "In Vivo",
  "versions": []
}