title: Ex vivo Ceftolozane/Tazobactam Clearance during Continuous Renal Replacement Therapy.
abstract: OBJECTIVE
  To determine ceftolozane/tazobactam transmembrane clearances (CLTM) in continuous hemofiltration (CHF) and continuous hemodialysis (CHD) and to determine optimal ceftolozane/tazobactam dosing regimens for patients receiving continuous renal replacement therapy (CRRT).
  
  
  METHODS
  Validated, ex vivo CHF and CHD bovine blood models using polysulfone (HF1400) and AN69 (Multiflow 150-M) hemofilters were used to evaluate adsorption and CLTM at different effluent flow rates. Monte Carlo simulations (MCS) using pharmacokinetic parameters from published studies and CLTM from this study were used to generate ceftolozane/tazobactam dosing for patients receiving CRRT.
  
  
  RESULTS
  CHF and CHD CLTM did not differ at equivalent effluent rates. CLTM approximated effluent flow rates. No adsorption of ceftolozane/tazobactam occurred for either hemofilter. Effluent flow was the most important determinant of MCS-derived doses.
  
  
  CONCLUSIONS
  CRRT clearances of ceftolozane/tazobactam depended on effluent flow rates but not hemofilter types. MCS-derived ceftolozane/tazobactam doses of 750 (500/250)-1,500 (1,000/500) mg every 8 h met pharmacodynamic targets for virtual patients receiving CRRT at contemporary effluent rates.
authors.affiliation: Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA.
authors.forename: Weerachai
authors.initials: W
authors.lastname: Chaijamorn
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Shaw
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Lewis
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Mueller
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002417:Cattle; D002511:Cephalosporins / Q000493:pharmacokinetics*; D054796:Drug Dosage Calculations; D015312:Hemodialysis Solutions / Q000737:chemistry; D006801:Humans; D008567:Membranes, Artificial; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D017582:Renal Replacement Therapy / Q000379:methods*; D000078142:Tazobactam
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D015312:Hemodialysis Solutions; D008567:Membranes, Artificial; C519491:ceftolozane; D010397:Penicillanic Acid; D000078142:Tazobactam