title: Ertapenem clearance during modeled continuous renal replacement therapy.
abstract: OBJECTIVE
  To determine ertapenem transmembrane clearance (CLtm) during continuous renal replacement therapy (CRRT) using a validated in vitro model.
  
  
  METHODS
  Ertapenem clearance during continuous hemofiltration and hemodialysis was assessed with AN69 and polysulfone hemodiafilters at 4 dialysate (Qd) and ultrafiltration rates (Quf): 1, 2, 3, and 6 l/hour. Blood and dialysate samples were collected at each flow rate and assayed for urea (control solute) and ertapenem concentrations. The experiment was repeated 5 times for each hemodiafilter type. Ertapenem and urea sieving coefficient (SC) and saturation coefficient (SA) were assessed, and CLtm calculated.
  
  
  RESULTS
  In continuous hemofiltration mode, urea and ertapenem SC ranged from 1.00 to 1.19 at all Quf and did not differ between hemodiafilter types. Consequently, convective CLtm also did not differ between hemodiafilters. In continuous dialysis mode, urea Cltm did not differ between hemodiafilter types at any Qd. However, ertapenem SA and CLtm were significantly different between hemodiafilter types at Qd 6l/hour (p<0.001). As Qd increased, mean +/- SD AN69 SA declined significantly from 0.87 +/- 0.12 at Qd 1 l/hour to 0.45 +/- 0.02 at Qd 6 l/hour (p<0.001). Ertapenem SA did not differ at any Qd with the polysulfone hemodiafilter (range 0.71-0.80).
  
  
  CONCLUSIONS
  Ertapenem was cleared substantially in these in vitro CRRT models. However, our findings illustrate discordance between our observed SC and SA and the published unbound fraction of ertapenem. This finding has been reported with many other drugs, including carbapenem antibiotics. If in vivo studies corroborate our SA and SC findings, dosage adjustment for patients receiving CRRT will be required.
authors.affiliation: Department of Clinical, Social and Administrative Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Stevenson
authors.forename: J H
authors.initials: JH
authors.lastname: Patel
authors.forename: M D
authors.initials: MD
authors.lastname: Churchwell
authors.forename: A M
authors.initials: AM
authors.lastname: Vilay
authors.forename: D D
authors.initials: DD
authors.lastname: Depestel
authors.forename: F
authors.initials: F
authors.lastname: Sörgel
authors.forename: M
authors.initials: M
authors.lastname: Kinzig
authors.forename: V
authors.initials: V
authors.lastname: Jakob
authors.forename: B A
authors.initials: BA
authors.lastname: Mueller
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D015314:Dialysis Solutions / Q000737:chemistry; D000077727:Ertapenem; D006440:Hemofiltration; D008567:Membranes, Artificial; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000378:metabolism* / Q000628:therapy; D013552:Swine; D047090:beta-Lactams / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D015314:Dialysis Solutions; D008567:Membranes, Artificial; D047090:beta-Lactams; D000077727:Ertapenem