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Supplementary Material for: Trimethoprim and Sulfamethoxazole Transmembrane Clearance during Modeled Continuous Renal Replacement Therapy

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posted on 16.12.2014, 00:00 by Kesner J.M., Yardman-Frank J.M., Mercier R.-C., Wong C.S., Walker S.E., Argyres D.P., Vilay A.M.
Background/Aims: 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.