Accumulation pharmacokinetics of tobramycin

Area of Science:

• Pharmacology
• Nephrology
• Clinical Pharmacy

Background:

• Tobramycin pharmacokinetics are typically modeled using a one-compartment model.
• This model inadequately explains incomplete urinary recovery and prolonged drug persistence post-treatment.

Purpose of the Study:

• To investigate the multiple-dose behavior of tobramycin in patients with stable renal function.
• To elucidate the reasons for incomplete urinary recovery and prolonged post-treatment drug persistence.

Main Methods:

• Analysis of peak and trough serum concentrations, urine recovery, and postmortem tissue concentrations.
• Application of a two-compartment pharmacokinetic model to describe drug disposition.

Main Results:

• Serum tobramycin concentrations exhibited a biphasic decline post-treatment, with a prolonged second-phase half-life (average 146 h).
• Tobramycin accumulated in patient tissues throughout treatment, irrespective of dosage.
• Complete urinary recovery required extended collection periods (10–20 days).

Conclusions:

• A two-compartment model accurately describes tobramycin's pharmacokinetics, accounting for tissue accumulation.
• Tissue accumulation explains rising serum concentrations during treatment and prolonged drug detection post-therapy.