Pharmacokinetics of 300 mg/d Intraperitoneal Daptomycin: New Insight from the DaptoDP Study

Abstract

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 in situ 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.

Keywords: Intraperitoneal route; continuous ambulatory peritoneal dialysis; peritoneal dialysis; peritoneal dialysis-related peritonitis; renal failure.