title: Trimethoprim and sulfamethoxazole transmembrane clearance during modeled continuous renal replacement therapy.
abstract: OBJECTIVE
  There is limited data regarding trimethoprim (TMP)/sulfamethoxazole (SMX) continuous renal replacement therapy (CRRT) dosing. We aimed to estimate TMP/SMX transmembrane clearance (CLtm) during continuous hemofiltration (CH) and continuous hemodialysis (CD) to guide dosing.
  
  
  METHODS
  Using an in vitro model, TMP/SMX sieving coefficients (SC) and saturation coefficients (SA) were determined with high-flux polyarylethersulfone and polyacrylonitrile-sodium methallyl sulfonate copolymer hemodiafilters at ultrafiltration/dialysate rates of 1, 2, 3, and 6 l/h. TMP/SMX CLtm was calculated using measured SC and SA. TMP/SMX CRRT doses were modeled using CLtm and published TMP/SMX pharmacokinetic parameters.
  
  
  RESULTS
  TMP SC/SA during CH/CD were significantly higher than SMX SC/SA. During modeling, TMP 10 mg/kg/day and its corresponding SMX dose, 50 mg/kg/day, resulted in steady state TMP/SMX peak concentrations associated with efficacy against Pneumocystis jirovecii.
  
  
  CONCLUSIONS
  CRRT resulted in greater TMP CLtm than SMX. TMP 10 mg/kg/day divided q12h may be an appropriate initial dose to consider in patients undergoing CRRT.
authors.affiliation: College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Kesner
authors.forename: Joseph Michael
authors.initials: JM
authors.lastname: Yardman-Frank
authors.forename: Renee-Claude
authors.initials: RC
authors.lastname: Mercier
authors.forename: Craig S
authors.initials: CS
authors.lastname: Wong
authors.forename: Scott E
authors.initials: SE
authors.lastname: Walker
authors.forename: Dean P
authors.initials: DP
authors.lastname: Argyres
authors.forename: Aloun Mary
authors.initials: AM
authors.lastname: Vilay
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D015314:Dialysis Solutions / Q000737:chemistry; D017583:Hemodiafiltration / Q000295:instrumentation; D006440:Hemofiltration / Q000295:instrumentation / Q000379:methods; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D008567:Membranes, Artificial; D008657:Metabolic Clearance Rate; D008956:Models, Chemical; D009994:Osmolar Concentration; D010539:Permeability; D006435:Renal Dialysis / Q000295:instrumentation / Q000379:methods*; D012709:Serum Albumin / Q000032:analysis; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000097:blood / Q000493:pharmacokinetics*; D014508:Urea / Q000097:blood
chemical_list: D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D015314:Dialysis Solutions; D006454:Hemoglobins; D008567:Membranes, Artificial; D012709:Serum Albumin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D014508:Urea