Amikacin Pharmacokinetics: Wide Interpatient Variation in 98 Patients

The disposition of amikacin was studied in 98 patients receiving treatment for severe gram‐negative sepsis. Several factors were identified which were significantly related to the drug's elimination rate. These included renal function (r = .67), age (r = –.55), distribution volume (r = .34), and weight (r = –.31). These variables explain 62% of the variance (R2) in elimination rate constant when combined in a multiple regression model. The drug's half‐life demonstrated considerable interpatient variation in patients with a normal serum creatinine (.68–14.4 hrs) or with a normal creatinine clearance (.68–7.2 hrs). The drug's distribution volume ranged from .08 to .48 L/Kg. The drug's clearance varied from 6.5 to 200 mL/hr/kg for patients with a normal serum creatinine and 17.8 to 200 mL/hr/kg for patients with a normal creatinine clearance. The interpatient variation in the drug's kinetic parameters is a concerning clinical problem. Measuring serum amikacin concentrations and adjusting dosage regimens are necessary to achieve desired peak and trough serum concentrations.