Dahl N V, Foote E F, Searson K M, Fein J L, Kapoian T, Steward C A, Sherman R A
College of Pharmacy, Rutgers, State University of New Jersey, Piscataway 09954, USA.
Ann Pharmacother. 1998 Dec;32(12):1284-9. doi: 10.1345/aph.18152.
To investigate the pharmacokinetic characteristics of intraperitoneal fluconazole in patients undergoing continuous cycling peritoneal dialysis (CCPD).
Prospective, nonrandomized, single-dose, open-label study.
Five noninfected volunteer CCPD patients.
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.
Fluconazole concentrations were assayed by gas-liquid chromatography. Pharmacokinetic parameters were calculated using standard noncompartmental techniques.
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.
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.
研究氟康唑腹腔内给药在持续循环腹膜透析（CCPD）患者中的药代动力学特征。
前瞻性、非随机、单剂量、开放标签研究。
5名未感染的CCPD志愿者患者。
患者在白天长时间留腹期间接受200mg氟康唑单次腹腔内给药。给药前及给药后1、3、6、12小时（首次留腹结束时）、24小时（过夜循环后）、48、72、96和120小时采集血样。在整个研究过程中收集用过的透析液。除非患者无尿，否则在最初48小时收集尿液。
采用气液色谱法测定氟康唑浓度。使用标准的非房室技术计算药代动力学参数。
氟康唑腹腔内给药在12小时留腹期间的生物利用度为96%±2%，吸收半衰期为2.5±1.2小时，血清消除半衰期为71.65±12.76小时，分布容积为0.66±0.13L/kg。腹膜清除率为5.96±0.93mL/min，与总透析液量成正比。肾脏清除率与肾脏肌酐清除率成正比。
目前真菌性腹膜炎的治疗指南建议每24小时腹腔内给予200mg氟康唑。我们的数据表明，每48小时给予该剂量足以使大多数念珠菌属的血清和腹膜浓度维持在最低抑菌浓度以上。其他因素，如残余肾功能和透析方案，也可能需要考虑。
