TRIMETHOPRIM-SULFAMETHOXAZOLE PHARMACOKINETICS IN TRAUMA PATIENTS

Study Objectives. To characterize the pharmacokinetic profile of trime thoprime-sulfamethoxazole (TMP-SMX) in trauma patients and to compare these parameter estimates With those obtained in nontrauma patients. D esign. Open-label, multidose, pharmacokinetic study. Setting. Trauma i ntensive care unit of a level 1 trauma center located within a regiona l medical center. Patients. Fifteen adult trauma patients with serious gram-negative infections. All patients were studied on day 1 of treat ment, nine on day 3, three on day 5, and two on day 7. One patient was discontinued from the study because of a possible drug-induced rash. Interventions. Study patients received TMP 4 mg/kg and SMX 20 mg/kg in travenously every 12 hours. Serial blood sampling was performed up to 4 times per patient between treatment days 1 and 7. Serum was assayed for TMP-SMX using high-performance liquid chromatography. A one-compar tment model was fit to the data using maximum likelihood estimation. M easurements and Main Results. Mean (SD) baseline parameter estimates f or TMP were volume 2.1 (0.65) L/kg, half-life 9.7 (3.0) hours, and cle arance 2.6 (0.80) ml/min/kg. Estimates for SMX were volume 0.51 (0.1 0 ) L/kg, half-life 7.8 (2.0) hours, and clearance 0.80 (0.29) ml/min/kg . Both volume (p<0.01) and clearance (p<0.001) for SMX were significan tly higher and half-life (p<0.05) significantly shorter than previousl y reported estimates in nontrauma patients. No significant differences in TMP parameter estimates were found. Neither TMP nor SMX clearance was significantly correlated with estimated creatinine clearance (p>0. 05). Conclusion. The results indicate that the pharmacokinetics of SMX in trauma patients differ significantly from nontrauma patients, whic h may result in lower than expected concentrations using standard dosi ng guidelines.