Pharmacokinetics of Intraperitoneal Daptomycin in Patients with Peritoneal Dialysis-Related Peritonitis.
♦ BACKGROUND: Antibiotics are preferentially delivered via the peritoneal route to treat peritoneal dialysis-related peritonitis (PDRP) to ensure that maximal concentrations are delivered to the site of infection. Our study focused on the pharmacokinetics of daptomycin (DAP) administered via the intraperitoneal (IP) route in patients with PDRP. ♦ METHODS: According to the DaptoDP protocol (Clinical Trial No. 2012-005699-33), IP DAP was administered daily, i.e., during the 6-h Nutrineal (Baxter Healthcare Corporation, Deerfield, IL, USA) dwell time period, for 14 days, in addition to administration of the antibiotics used for the usual care of patients with PDRP. The plasma and IP levels of DAP were measured on days 1 and 5. The tested dose was 200 mg/day. The principal endpoint was the dialysate concentration after 6 hours of dwell time > 16 mg/L (corresponding to 4 x minimum inhibitory concentration [MIC] for E. faecalis). ♦ RESULTS: Three participants were evaluated. On day 5, the IP concentrations after 6 hours of dwell time were between 6.3 and 23.4 mg/L, and the peak plasma concentrations were between 13.0 and 15.3 mg/L. ♦ CONCLUSION: The results suggest that 200 mg/day is very likely sufficient for the treatment of PDRP by Staphylococci or Streptococci whereas it could be insufficient to treat PRDP by Enterococci. The good peritoneal bioavailability of DAP was quantitatively established, suggesting that IP administration could also be used as an alternate route for patients with damaged venous access. No DAP accumulation that could lead to toxic concentrations after repeated administration is expected, even in anuric patients. The protocol will further continue to assess whether a higher dose achieves the pharmacokinetic objectives.
Clinical Research Department, CHU de Caen, France peyrosaintpaul-l@chu-caen.fr.
Laure
L
Peyro Saint Paul
Nephrology Department, CHU de Caen, France.
Maxence
M
Ficheux
Pharmacology Department, CHU de Caen, France.
Danièle
D
Debruyne
Pharmacology Department, CHU de Caen, France.
Magalie
M
Loilier
Nephrology Department, CHU de Caen, France.
Nicolas
N
Bouvier
Clinical Research Department, CHU de Caen, France.
Rémy
R
Morello
Clinical Research Department, CHU de Caen, France.
Jean-Jacques
JJ
Parienti
Infectiology Department, CHU de Caen, France.
Renaud
R
Verdon
Clinical Research Department, CHU de Caen, France.
François
F
Fournel
Microbiology Department, CHU de Caen, France.
Vincent
V
Cattoir
Nephrology Department, CHU de Caen, France.
Thierry
T
Lobbedez
D000368:Aged; D017576:Daptomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005602:France; D006801:Humans; D007274:Injections, Intraperitoneal; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D010530:Peritoneal Dialysis / Q000009:adverse effects* / Q000379:methods; D010538:Peritonitis / Q000188:drug therapy* / Q000209:etiology* / Q000382:microbiology; D012494:Sampling Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
D017576:Daptomycin
Daptomycin; gram-positive infection; intraperitoneal; peritoneal dialysis; peritoneal dialysis-related peritonitis; pharmacokinetics