[Threshold doses in ototoxicity].

Area of Science:

• Pharmacology
• Toxicology
• Ototoxicology

Context:

• Aminoglycoside antibiotics are widely used but carry a risk of ototoxicity.
• Understanding dose-dependent ototoxicity is crucial for patient safety.
• Identifying threshold doses helps in managing treatment risks.

Purpose:

• To stress the importance of total administered aminoglycoside dose in ototoxicity.
• To define clinical and absolute ototoxicity threshold doses for modern aminoglycoside antibiotics.
• To provide specific threshold dose values for gentamicin and amikacin.

Summary:

• The risk of irreversible ototoxic damage from aminoglycosides is low (<2%) within clinical dose ranges for patients without additional risk factors.
• The risk decreases further (<0.2%) within the absolute ototoxicity range.
• Based on clinical and experimental data, threshold doses were determined: gentamicin (50 mg/kg clinical, 20 mg/kg absolute) and amikacin (120 mg/kg clinical, 50 mg/kg absolute).

Impact:

• Provides critical data for clinicians to minimize ototoxicity risk when prescribing aminoglycosides.
• Establishes evidence-based guidelines for safe aminoglycoside dosing.
• Contributes to the understanding of aminoglycoside-induced ototoxicity and its management.