383 Pharmacokinetics of Trimethoprim-Sulfamethoxazole in a Burn Patient on Continuous Venovenous Hemofiltration

Abstract Introduction Pharmacokinetics (PK) can be significantly impacted by altered organ function, the use of continuous venovenous hemofiltration (CVVH), and physiologic and metabolic changes that occur in critically ill burn patients. To date, there are no reports describing the PK of trimethoprim (TMP)/sulfamethoxazole (SMX) in burn patients receiving CVVH. We determined TMP and SMX PK parameters in one burn patient receiving CVVH. Methods Plasma and ultrafiltrate samples were obtained 0.5, 2, and 4 hours after the end of drug infusion, and prior to the next dose. TMP and SMX concentrations were determined by HPLC. PK parameters were estimated using non-compartmental analysis (WinNonLin, Certara Inc.). The sieving coefficient (Sc), representing the fraction of TMP and SMX crossing the filter membrane, and clearance attributable to CVVH were calculated. Results The 49 y/o male patient with 32% TBSA burns received TMP/SMX 500mg/2500mg IV q8h (TMP 15 mg/kg/day), infused over 90 minutes, for Stenotrophomonas maltophilia pneumonia. The patient was initiated on CVVH for volume management and renal impairment, manifesting as acidemia, uremia, and hyperkalemia. He received an average CVVH dose of 23.8 ± 2.0 mL/kg/h. PK parameters for TMP/SMX were determined (see table). Values for total TMP could not be calculated and were estimated from free TMP values, assuming protein binding of 65%. The terminal SMX data point was excluded from analysis, as it deviated above the decay curve. Conclusions These preliminary PK values are the first published for TMP/SMX in a burn patient on CVVH, demonstrating discordant PK values between the antimicrobial and the inhibitor. Additional data are required to characterize the impact of CVVH on the PK of TMP/SMX in burn patients and optimize its dosing. Applicability of Research to Practice Ensuring optimal PK/PD of antibiotic agents in critically ill burn patients may improve survival in this population with many physiologic disturbances which can undermine the effectiveness of therapy. Pharmacokinetic Parameters of TMP and SMX Total TMP Free TMP Total SMX Free SMX Cmax(µg/mL) 11.7 7.6 62.7 17.6 AUC0→8 (h●µg/mL) 86.5 56.2 436.7 243.4 t½ (h) 57.1 54.3 10.3 3.7 Ke (h-1) 0.012 0.013 0.067 0.189 Vss (L) 2405 3522.3 116.7 76.4 Vss (L/kg) 22.7 33.2 1.1 0.7 CLss (L/h) 28.9 44.5 5.7 10.3 CLss (mL/kg/min) 4.54 7 0.89 1.62 Mean % Free ± SD 34.9 ± 7.7 60.3 ± 13.1 Mean SC ± SD 0.61 ± 0.21 0.56 ± 0.22 CLCVVH (L/h) 0.012 0.01 % CLCVVH 0.04% 0