Aminoglycoside Pharmacokinetics in Patients with AIDS

Abstract

Objective To determine the pharmacokinetic parameters of aminoglycosides in patients with AIDS and to compare these parameters with those of a control group of patients not infected with HIV. Design Retrospective, chart-review study. Patients Nineteen AIDS patients and 19 non-HIV-infected patients (control) were identified through a review of pharmacokinetic monitoring cards. Methods Patients’ charts were reviewed for demographic data, aminoglycoside (gentamicin, tobramycin, and amikacin) dosing schedule, and steady-state peak and trough concentrations. Pharmacokinetic parameters were calculated using a one-compartment open model. Results Significant differences were found in the elimination rate constant (Ke) between the two groups (mean ± SD, 0.20 ± 0.084/h in the AIDS group and 0.26 ± 0.095/h in the control group). Half-life was significantly longer in the AIDS group versus controls (4.3 ± 2.5 and 2.99 ± 1.15/h, respectively). The volume of distribution (Vd), expressed in terms of liters and liters per kilogram total body weight (TBW), was significantly larger in the AIDS group than in the control group (28.3 ± 14 L [0.43 ± 0.21 L/kg TBW] and 19.2 ± 4.95 L [0.28 ± 0.07 L/kg TBW], respectively). Clearance in terms of liters per hour and Vd in terms of L/kg ideal body weight were not significantly different between the two groups. Albumin was similar in both groups (34 ± 7 g/L, control group; 28 ± 7 g/L, AIDS group). Conclusions Aminoglycoside pharmacokinetics were found to be altered in the patients with AIDS. When calculating an initial dose of an aminoglycoside in AIDS patients, use of estimated normal population parameters may result in lower peaks in these individuals. Pharmacokinetic parameters may need to be adjusted in AIDS patients because of their large Vd and slower Ke.