Pharmacokinetics of intraperitoneal fluconazole during continuous cycling peritoneal dialysis

OBJECTIVE: To investigate the pharmacokinetic characteristics of intraperit oneal fluconazole in patients undergoing continuous cycling peritoneal dial ysis (CCPD). DESIGN: Prospective, nonrandomized, single-dose, open-label study. PARTICIPANTS: Five noninfected volunteer CCPD patients. INTERVENTIONS: Patients received a single dose of intraperitoneal fluconazo le 200 mg during their long daytime dwell. Blood samples were collected bef ore and 1, 3, 6, 12 (end of first dwell), 24 (after overnight cycling), 48, 72, 96, and 120 hours after dosing. Used dialysate was collected throughou t the study. Unless the patient was anuric, urine was collected for the fir st 48 hours. MAIN OUTCOME MEASURE: Fluconazole concentrations were assayed by gas-liquid chromatography. Pharmacokinetic parameters were calculated using standard noncompartmental techniques. RESULTS: The bioavailability of intraperitoneal fluconazole was 96% +/- 2% over a 12-hour dwell, absorption half-life was 2.5 +/- 1.2 hours, serum eli mination half-life was 71.65 +/- 12.76 hours, and volume of distribution wa s 0.66 +/- 0.13 L/kg. Peritoneal clearance was 5.96 +/- 0.93 mL/min and pro portional to total dialysate volume. Renal clearance was proportional to re nal creatinine clearance. CONCLUSIONS: Current treatment guidelines for fungal peritonitis suggest fl uconazole 200 mg intraperitoneally every 24 hours. Our data suggest that th is dose, administered every 48 hours, is more than sufficient to maintain s erum and peritoneal concentrations above the minimum inhibitory concentrati on for most Candida spp. Other factors, such as residual renal function and dialysis prescription, may also need to be considered.