Trimethoprim-sulfamethoxazole pharmacokinetics in trauma patients

To characterize the pharmacokinetic profile of trimethoprim-sulfamethoxazole (TMP-SMX) in trauma patients and to compare these parameter estimates with those obtained in nontrauma patients.

Open-label, multidose, pharmacokinetic study.

Trauma intensive care unit of a level 1 trauma center located within a regional medical center.

Fifteen adult trauma patients with serious gram-negative infections. All patients were studied on day 1 of treatment, 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.

Study patients received TMP 4 mg/kg and SMX 20 mg/kg intravenously 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-compartment model was fit to the data using maximum likelihood estimation.

Mean (SD) baseline parameter estimates for TMP were volume 2.1 (0.65) L/kg, half-life 9.7 (3.0) hours, and clearance 2.6 (0.80) ml/min/kg. Estimates for SMX were volume 0.51 (0.10) 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 significantly higher and half-life (p < 0.05) significantly shorter than previously 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).

The results indicate that the pharmacokinetics of SMX in trauma patients differ significantly from nontrauma patients, which may result in lower than expected concentrations using standard dosing guidelines.