Variability of tobramycin pharmacokinetics in cystic fibrosis

This study determined the extent and impact of tobramycin pharmacokinetic variability in cystic fibrosis patients. Twenty patients were hospitalized twice and the tobramycin half-life, volume of distribution and clearance were determined during Weeks 1 and 2 of both admissions. A difference (P less than 0.05) existed between Weeks 1 and 2 of each admission, but not between admissions, for the clearance and half-life. No difference existed between weeks or admissions for the volume of distribution. No significant correlations existed between weeks within an admission for the half-life and clearance. There was a significant correlation for the volume of distribution between Weeks 1 and 2 of the second admission but not for the first admission. The percents of coefficient of variation and ranges were large. With dosing regimens derived from previously determined factors, "within admission" predicted peaks and troughs would result in 60 and 35% of patients outside the therapeutic range for Admissions 1 and 2, respectively. "Between admission" predictions would result in 65 and 75% of patients outside the therapeutic range. We conclude that considerable variability exists and recommend weekly determinations of serum concentrations and dosing adjustments.