CAN PHARMACOKINETIC DOSING DECREASE NEPHROTOXICITY ASSOCIATED WITH AMINOGLYCOSIDE THERAPY

A randomized, controlled clinical trial was performed to determine whe ther individualized dosing by use of Bayesian pharmacokinetic modeling could decrease nephrotoxicity accosted with aminoglycoside therapy. T wo hundred forty-three patients receiving aminoglycosides for suspecte d or proven infection were randomly assigned to one of three groups: u sual physician-directed dosing (Group 1), pharmacist-assisted dosing ( Group 2), or pharmacist-directed dosing (Group 3). Dosing in Groups 2 and 3 was based on a Bayesian pharmacokinetic dosing program, whereas Group 1 served as the control group. Individualized dosing resulted in higher mean postinfusion (peak) serum aminoglycoside levels, higher r atios of mean peak level to minimum-inhibitory concentration (peak/MIC ratios), and a trend toward lower trough serum levels. Milligrams per dose were higher and number of doses per day was lower in the pharmac ist-dosed groups. However, the incidence of nephrotoxicity (greater-th an-or-equal-to 100% increase in serum creatinine) was not different am ong the three groups (16, 27, and 16% in Groups 1, 2, and 3, respectiv ely). Similarly, severity of toxicity was not affected by the dosing i ntervention. Risk factors for toxicity included duration of therapy, s hock, treatment with furosemide, older age, and liver disease. After c ontrolling for these factors, the dosing intervention still had no eff ect on nephrotoxicity. It was concluded that Bayesian pharmacokinetic dosing did not decrease the risk of nephrotoxicity associated with ami noglycoside therapy.