Saint Paul Laure Peyro, Ficheux Maxence, Debruyne Danièle, Loilier Magalie, Bouvier Nicolas, Morello Rémy, Verdon Renaud, Le Blanc Elsa, Cattoir Vincent, Lobbedez Thierry
Clinical Research Department, CHU de Caen, Caen, FRANCE
Nephrology Department, CHU de Caen, Caen, FRANCE.
Perit Dial Int. 2018 Nov-Dec;38(6):463-466. doi: 10.3747/pdi.2017.00256.
The DaptoDP (NCT 2012-005699-33) study aimed to evaluate the pharmacokinetic parameters of daptomycin (DAP) in peritoneal dialysis-related peritonitis (PDRP) patients following intraperitoneal (IP) administration. The authors have already reported the findings on the 200-mg dosing and present here the follow-up results of the 300-mg dosing. The primary endpoint was a dialysate concentration of DAP above the effective concentration during 6 hours of dwell time i.e., 16 mg/L. Secondary endpoints were to avoid the toxic threshold of 120 mg/L DAP and to be above 16 mg/L DAP for 2 hours in plasma. Pharmacokinetic parameters were evaluated on days 1 and 5. Safety data were evaluated on days 1 to 14 based on clinical and biological parameters. Daptomycin was administered in Nutrineal during 6 hours of dwell time for 14 days plus the usual antibiotic therapy in a separate dwell. Because the 200-mg dosing objectives were not reached, a higher DAP dose of 300 mg was tested in the next 3 patients. Effective dialysate and plasma concentrations were achieved at the 300-mg DAP dose with the plasma concentration well below the toxic threshold, even at steady state, during which the accumulation factor never exceeded 3. The optimal DAP dose of 300 mg daily by the IP route, as determined by the pharmacokinetic data, needs to be clinically confirmed prior to routine use. The peritoneal bioavailability of DAP supports using the IP route as an alternative to the intravenous route for peritonitis and systemic infections.
达普托DP（NCT 2012 - 005699 - 33）研究旨在评估腹腔内（IP）给药后，达托霉素（DAP）在腹膜透析相关腹膜炎（PDRP）患者中的药代动力学参数。作者已报告了200mg剂量的研究结果，本文呈现300mg剂量的后续结果。主要终点是在6小时驻留时间内，透析液中DAP浓度高于有效浓度，即16mg/L。次要终点是避免DAP的120mg/L毒性阈值，并使血浆中DAP在2小时内高于16mg/L。在第1天和第5天评估药代动力学参数。基于临床和生物学参数，在第1天至第14天评估安全性数据。达托霉素在Nutrineal中于6小时驻留时间内给药，共14天，外加在单独驻留时间内进行的常规抗生素治疗。由于未达到200mg剂量目标，接下来的3名患者接受了更高的300mg DAP剂量测试。在300mg DAP剂量下，即使在稳态时血浆浓度远低于毒性阈值，也达到了有效的透析液和血浆浓度，此时蓄积因子从未超过3。根据药代动力学数据确定的每日300mg IP途径的最佳DAP剂量，在常规使用前需要进行临床确认。DAP的腹膜生物利用度支持将IP途径作为腹膜炎和全身感染时静脉途径的替代方法。
