What is the recommended dose regimen for intravenous (IV) glutathione administration?

IV Glutathione Dosing Regimen

For chemotherapy-induced peripheral neuropathy prevention, administer 1,500 mg/m² IV over 15 minutes immediately before each chemotherapy infusion, based on the most consistent evidence from multiple randomized controlled trials. 1

Evidence-Based Dosing by Clinical Indication

Chemotherapy-Induced Neuropathy Prevention

Standard Dose:

• 1,500 mg/m² diluted in 100 mL saline, infused over 15 minutes immediately before platinum-based or taxane chemotherapy 1
• This regimen demonstrated significant reduction in grade 3-4 neurotoxicity (0% vs 26%, P=0.01) with oxaliplatin 1
• Reduced neuropathy incidence from 88% to 17% after 15 weeks with cisplatin (P<0.001) 1

Alternative Dosing Regimens Studied:

• 2.5 g IV over 15 minutes for cisplatin-based regimens 1
• 3 g/m² IV over 20 minutes before cisplatin (improved symptom scores, P=0.05) 1
• 5 g IV bolus immediately before cisplatin (no significant benefit demonstrated) 1

Acute Myocardial Infarction

Loading and Maintenance Protocol:

• 2,500 mg IV over 10 minutes immediately before primary angioplasty 2
• Followed by 2,500 mg IV at 24,48, and 72 hours post-procedure 2
• This regimen significantly reduced NOX2 activation (P<0.0001), inflammatory markers (P<0.0001), and cardiac troponin release (P<0.0001) 2

Parkinson's Disease Symptom Management

Empirical Dosing (Limited Evidence):

• 1,400 mg IV administered 2-3 times weekly for tremor and rigidity management 3
• Evidence is anecdotal; no standardized dosing exists for this indication 3

Critical Pharmacokinetic Considerations

Oral Administration is Ineffective:

• Oral glutathione has negligible systemic bioavailability due to intestinal and hepatic gamma-glutamyltransferase hydrolysis 4
• Even 3 g oral doses fail to increase plasma glutathione concentrations 4
• IV administration is mandatory for therapeutic effect 4

Preparation and Compatibility

Compatible Solutions:

• 0.9% normal saline 5
• 5% dextrose solution 5
• Propofol 10 mg/mL 5

Incompatible Solutions:

• Avoid Normosol-M with 5% glucose due to sodium bisulfite interference 5

Stability:

• Maintains antioxidant properties for 24 hours when properly diluted 5
• Prepare immediately before administration when possible 5

Administration Timing

For Chemotherapy Protection:

• Administer immediately before chemotherapy infusion (within 15-20 minutes prior) 1
• Continue with each chemotherapy cycle throughout treatment 1

For Acute Cardiac Events:

• First dose before intervention, then every 24 hours for 72 hours total 2

Important Caveats

Paclitaxel/Carboplatin Regimens:

• Glutathione showed no significant advantage for paclitaxel-induced neuropathy (P=0.449) 1
• Weekly paclitaxel schedules may actually favor placebo over glutathione (P=0.002) 1
• Consider alternative neuroprotective strategies for taxane-based regimens 1

Dose-Limiting Toxicity:

• When combined with escalating cisplatin doses, nephrotoxicity occurred at cisplatin 175 mg/m² despite glutathione co-administration 6
• Ototoxicity (44% of patients) and severe nausea/vomiting (35% of cycles) remained problematic 6
• Glutathione does not eliminate all platinum-related toxicities 6

Contraindication in Critical Illness:

• High-dose parenteral glutamine (not glutathione) is contraindicated in critically ill patients with kidney failure based on REDOX trial data 1
• This does not apply to glutathione, but highlights the importance of distinguishing these compounds 1

Monitoring Parameters

• Baseline and serial assessment of neuropathy using validated scales (NCI-CTC, EORTC-QLQ-CIPN20) 1
• Renal function monitoring when combined with nephrotoxic chemotherapy 6
• Cardiac biomarkers and inflammatory markers if used for myocardial infarction 2