Population pharmacokinetics of aminoglycoside antibiotics in patients with cystic fibrosis.

Abstract

The population pharmacokinetics of gentamicin and tobramycin were investigated in a group of 51 young adults with cystic fibrosis. Their ages ranged from 14-35 years, weights from 38-82 kg, and 27 of the patients were female. None of the patients had renal impairment, but 3 patients were treated in the intensive therapy unit (ITU) during one of their courses of therapy. Data comprised 219 courses of therapy and 544 concentrations (mean: 11 per patient). Concentration-time data were analyzed using a nonlinear mixed-effects model package (NONMEM) and were best described by a one-compartment model. Factors identified as potentially influencing aminoglycoside pharmacokinetics were added in a stepwise fashion and the best model found that drug clearance and volume of distribution were related to body surface area and admission to ITU. The mean population estimates were a clearance of 2.89 L/hr/m2 and a volume of distribution of 9.21 L/m2 with a 60% increase in patients who were admitted to ITU. Interpatient variability in clearance and volume were 14% and 8%, respectively. The results suggested that a dose of 120 mg/m2 should achieve an average 1 hour postdose peak of 10 mg/L and trough of <1 mg/L and that higher doses might be required in ITU patients.