POPULATION PHARMACOKINETICS AND RENAL FUNCTION-SPARING EFFECTS OF AMPHOTERICIN-B COLLOIDAL DISPERSION IN PATIENTS RECEIVING BONE-MARROW TRANSPLANTS

The purpose of this study was to evaluate the pharmacokinetics of amph otericin B colloidal dispersion and its effect on creatinine clearance in bone marrow transplant patients with systemic fungal infections. S eventy-five patients (42 females and 33 males) with a median age of 34 .5 years and a median weight of 70.0 kg were enrolled in the study, Pa tients received 1 of 15 dose levels (range, 0.5 to 8.0 mg/kg of body w eight) daily for a mean duration of 28 days and a mean cumulative dose amount of 8 g. Plasma samples for amphotericin B determination (media n number, 4; range, 2 to 30) and daily serum creatinine values were ob tained for each patient. Iterative two-stage analysis, one of several approaches to population pharmacokinetic and pharmacodynamic modelling , was employed for the pharmacokinetic analysis, The plasma data were available for 51 of 75 patients and were best described by a two-compa rtment model, Both plasma clearance and volume of distribution increas ed with escalating doses; the overall average terminal elimination hal f-life was 29 h, Of the covariates studied, only body weight and dose size were significant. Serum creatinine values over the duration of th erapy were available for 59 of 75 patients, Overall, there was no net change in renal function over the duration of therapy; 12 patients had >30% increases in creatinine clearance, whereas 13 had >30% decreases , No measure of amphotericin B colloidal dispersion exposure, demograp hic values, or concomitant treatment with other medications was relate d to changes in the creatinine clearance.