OBJECTIVE: To investigate the pharmacokinetic characteristics of intraperitoneal fluconazole in patients undergoing continuous cycling peritoneal dialysis (CCPD). DESIGN: Prospective, nonrandomized, single-dose, open-label study. PARTICIPANTS: Five noninfected volunteer CCPD patients. INTERVENTIONS: Patients received a single dose of intraperitoneal fluconazole 200 mg during their long daytime dwell. Blood samples were collected before 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 throughout the study. Unless the patient was anuric, urine was collected for the first 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 elimination half-life was 71.65 +/- 12.76 hours, and volume of distribution was 0.66 +/- 0.13 L/kg. Peritoneal clearance was 5.96 +/- 0.93 mL/min and proportional to total dialysate volume. Renal clearance was proportional to renal creatinine clearance. CONCLUSIONS: Current treatment guidelines for fungal peritonitis suggest fluconazole 200 mg intraperitoneally every 24 hours. Our data suggest that this dose, administered every 48 hours, is more than sufficient to maintain serum and peritoneal concentrations above the minimum inhibitory concentration for most Candida spp. Other factors, such as residual renal function and dialysis prescription, may also need to be considered.
OBJECTIVE: To investigate the pharmacokinetic characteristics of intraperitoneal fluconazole in patients undergoing continuous cycling peritoneal dialysis (CCPD). DESIGN: Prospective, nonrandomized, single-dose, open-label study. PARTICIPANTS: Five noninfected volunteer CCPD patients. INTERVENTIONS:Patients received a single dose of intraperitoneal fluconazole 200 mg during their long daytime dwell. Blood samples were collected before 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 throughout the study. Unless the patient was anuric, urine was collected for the first 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 elimination half-life was 71.65 +/- 12.76 hours, and volume of distribution was 0.66 +/- 0.13 L/kg. Peritoneal clearance was 5.96 +/- 0.93 mL/min and proportional to total dialysate volume. Renal clearance was proportional to renal creatinine clearance. CONCLUSIONS: Current treatment guidelines for fungal peritonitis suggest fluconazole 200 mg intraperitoneally every 24 hours. Our data suggest that this dose, administered every 48 hours, is more than sufficient to maintain serum and peritoneal concentrations above the minimum inhibitory concentration for most Candida spp. Other factors, such as residual renal function and dialysis prescription, may also need to be considered.
Authors: Philip Kam-Tao Li; Cheuk Chun Szeto; Beth Piraino; Javier de Arteaga; Stanley Fan; Ana E Figueiredo; Douglas N Fish; Eric Goffin; Yong-Lim Kim; William Salzer; Dirk G Struijk; Isaac Teitelbaum; David W Johnson Journal: Perit Dial Int Date: 2016-06-09 Impact factor: 1.756