Tobramycin pharmacokinetics in very low birth weight infants

Area of Science:

• Neonatal Pharmacology
• Pediatric Infectious Diseases
• Clinical Pharmacy

Background:

• Standard tobramycin dosing (2.5 mg kg-1 12h-1) often leads to excessive trough serum concentrations (>2 mg L-1) in neonates.
• Limited data exists for optimal tobramycin dosing in infants weighing less than 1,000 g at birth.

Purpose of the Study:

• To evaluate a modified tobramramycin dosing regimen in very low birth weight infants.
• To determine if altered dosing intervals achieve safe and effective tobramycin serum concentrations.

Main Methods:

• Eight newborn infants (gestational age 24-30 weeks; birth weight 0.60-0.97 kg) received modified tobramycin doses.
• Dosing regimens included 2.5 mg kg-1 every 18 hours or 3.0 mg kg-1 every 24 hours.
• Tobramycin peak and trough serum concentrations were monitored.

Main Results:

• Peak serum concentrations ranged from 6.0-10.8 mg L-1, and trough concentrations ranged from 1.2-2.4 mg L-1.
• No infants had trough concentrations above 2 mg L-1 at 24 hours.
• Pharmacokinetic parameters (clearance, volume of distribution, half-life) were determined.

Conclusions:

• Modified tobramycin dosing regimens (2.5 mg kg-1 18h-1 or 3.0 mg kg-1 24h-1) are more acceptable than the current standard.
• These regimens achieve effective and safe peak and trough tobramycin serum concentrations in neonates weighing less than 1 kg.
• This approach improves tobramycin safety for high-risk neonatal populations.