L-Glutamine for Pediatric Sickle Cell Disease: Pharmacology, Mechanism of Action, Safety and Efficacy
- 1Division of Pediatric Hematology-Oncology, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, U.S.A.
- 2The Lundquist Institute for Biomedical Innovation, Torrance, CA, U.S.A.
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.
Materials 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.
Results: 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.
Conclusion: 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.
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BibTeX
@article{panosyan2026lglutamine,
title = {{L-Glutamine for Pediatric Sickle Cell Disease: Pharmacology, Mechanism of Action, Safety and Efficacy}},
author = {EDUARD H. PANOSYAN},
journal = {In Vivo},
year = {2026},
month = oct,
doi = {10.21873/invivo.14475},
url = {https://doi.org/10.21873/invivo.14475},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - L-Glutamine for Pediatric Sickle Cell Disease: Pharmacology, Mechanism of Action, Safety and Efficacy
AU - EDUARD H. PANOSYAN
PY - 2026
DA - 2026/10/29
JO - In Vivo
DO - 10.21873/invivo.14475
UR - https://doi.org/10.21873/invivo.14475
AB - 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. Materials 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. Results: 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. Conclusion: 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.
SN - 0258-851X
SN - 1791-7549
ER -