Gentamicin dosage requirements: wide interpatient variations in 242 surgery patients with normal renal function

Abstract

Wide interpatient variations were demonstrated in gentamicin elimination rate and dosage requirements for 242 surgery patients with normal renal function. These patients' half-lives ranged from 0.4 to 13.4 hours as compared to previous reports of 2.5 to 4 hours. The distribution volumes ranged from 0.06 to 0.63 liter/kg, as compared of reported values of 0.20 to 0.25 liter/kg. These wide interpatient variations in kinetic parameters, combined with the need to obtain narrow ranges in serum concentrations, necessitated measuring serum concentrations and individually calculating each patient's dosage regimen early in the treatment course. Using this approach, optimal peak and trough serum levels were consistently produced in these patients. Their required dosage regimens demonstrated considerable variability--ranging from 0.7 to 12.4 mg/kg/day. Compared to the recommended regimen (3 to 5 mg/kg/day), 47% of these surgery patients required higher dosages, and 14% required lower dosages. The incidence of ototoxicity and nephrotoxicity were extremely low, with only three patients possibly having gentamicin-associated nephrotoxicity. These results further emphasize the need to measure serum concentrations and make necessary dosage adjustments to ensure therapeutic levels. However, because of the wide interpatient variation, these increased dosage regimens are not routinely suggested without previously measuring serum concentrations.