Tobramycin elimination rate change from first to later doses in older cystic fibrosis patients

Adults with cystic fibrosis frequently require larger than usual tobramycin dosages in order to achieve desired serum concentrations. The application of dosing methods utilizing first-dose pharmacokinetics has been advocated as a means for rapidly attaining therapeutic serum concentrations. Review of ten cystic fibrosis patients between ages 13 and 33 years admitted for exacerbation of pulmonary disease caused primarily by Pseudomonas aeruginosa (Staphylococcus aureus in two patients) was conducted. Elimination rate constant (ke, h-1) was calculated from two concentration-time pairs obtained following the first dose. Two concentration-time pairs were again measured between cumulative doses (n) 7 to 19, and ke was calculated. First dose ke varied significantly from nth dose ke (p = 0.018). First-dose pharmacokinetic analysis may not be a reliable predictor of maintenance tobramycin dosage requirements due to apparent changes in ke over time.