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.