Direct Determination of Tobramycin Clearance in Patients with Mild-to-Moderate Cystic Fibrosis

Abstract

Studies performed in patients with cystic fibrosis (CF) have suggested altered pharmacokinetic parameters for aminoglycosides. Specifically, increased plasma clearance (CI) of aminoglycosides and increased apparent volume of distribution have been noted. In the present study, tobramycin CI is determined by both serum concentration data and direct renal clearance (Cl_ren). Tobramycin Cl_ren appeared to be directly correlated to the measured creatinine clearance (Cl_cr) (r = 0.93, p <0.01 ). The tobramycin Cl, by both methods of determination, was not elevated in comparison to the Cl_cr or expected values for patients without the disease. These results appear to corroborate a recent study in which the renal and plasma Cl of gentamicin was measured in patients with mild-to-moderate CF and were not noted to be elevated. It is suggested that standard doses of tobramycin be used initially in patients with mild-to-moderate CF with dosage adjustment based on serum concentration data to achieve the desired goals.