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.
Zaske
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College of Pharmacy, School of Medicine, University of Minnesota, St. Paul-Ramsey Medical Center 55101.
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Kohls
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000583:Amikacin / Q000097:blood / Q000493:pharmacokinetics*; D001424:Bacterial Infections / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D005260:Female; D006090:Gram-Negative Bacteria; D006207:Half-Life; D006801:Humans; D007223:Infant; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012044:Regression Analysis
D000583:Amikacin; D003404:Creatinine