L-GLUTAMINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for L-GLUTAMINE (L-GLUTAMINE).
L-glutamine is a conditionally essential amino acid that serves as a precursor for nucleotide synthesis, glutathione production, and energy metabolism. It modulates heat shock protein expression, supports intestinal epithelial cell proliferation, and attenuates glutamine metabolism in cancer cells, particularly in hematologic malignancies.
| Metabolism | L-glutamine is metabolized primarily in the liver and kidneys via glutaminase to glutamate and ammonia. It also undergoes transamination via aminotransferases. The small intestine and immune cells utilize glutamine for energy and biosynthesis. Excretion of metabolites occurs via urine. |
| Excretion | Renal: ~5-10% unchanged; biliary/fecal: negligible; majority metabolized by enterocytes and liver to glutamate, ammonia, and other amino acids. |
| Half-life | Terminal half-life approximately 1.5-2 hours in adults; clinically, enteral supplementation requires frequent dosing to maintain plasma levels. |
| Protein binding | Negligible (<5%); not significantly bound to plasma proteins. |
| Volume of Distribution | Approximately 0.3-0.5 L/kg (total body water); clinical note: distributes widely in muscle and other tissues, with higher concentrations in intracellular compartments. |
| Bioavailability | Oral: approximately 50-70% due to first-pass metabolism in enterocytes and liver; intravenous: 100%. |
| Onset of Action | Oral: ~30-60 minutes (increase in plasma glutamine levels); intravenous: immediate (seconds to minutes). |
| Duration of Action | Oral: 2-4 hours (plasma levels return to baseline); clinical effect duration depends on metabolic demand, typically 3-4 hours post-oral dose. |
Oral: 10-15 g three times daily (30-45 g/day). Powder dissolved in beverage. For sickle cell disease: 0.3 g/kg twice daily (max 30 g/day).
| Dosage form | FOR SOLUTION |
| Renal impairment | No specific dosing adjustment guidelines for renal impairment; use with caution in severe renal impairment due to potential accumulation of ammonia metabolites. |
| Liver impairment | Child-Pugh A-B: No adjustment. Child-Pugh C: Consider reducing dose to 10 g twice daily due to risk of hepatic encephalopathy from ammonia production. |
| Pediatric use | Sickle cell disease (≥5 years): 0.3 g/kg twice daily (max 30 g/day). Other indications: 0.3-0.5 g/kg/day divided three times daily. |
| Geriatric use | Initiate at lower end of dosing range (10 g twice daily) due to age-related decline in renal function and increased risk of adverse effects; monitor ammonia levels. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for L-GLUTAMINE (L-GLUTAMINE).
| Breastfeeding | Not recommended. Excreted in breast milk; M/P ratio unknown. Potential for neurological effects in neonate. Consider alternative if breastfeeding. |
| Teratogenic Risk | Pregnancy Category C. Insufficient human data; animal studies not reported. Theoretical risk due to role in neurotransmission and cell proliferation. Use only if benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to L-glutamine or any component of the formulation; severe hepatic impairment with history of encephalopathy; patients with Reye's syndrome; caution in patients with renal impairment.
| Precautions | Monitor for hepatic encephalopathy in patients with hepatic impairment; use with caution in patients with renal impairment due to potential ammonia accumulation; may cause gastrointestinal disturbances; avoid in patients with hypersensitivity to glutamine. |
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| Monitor maternal renal function and ammonia levels if high doses used. No specific fetal monitoring indicated. |
| Fertility Effects | No data on human fertility effects. In animal studies, no adverse reproductive effects reported. |