Evaluation of Sulfamethoxazole Concentrations in Treatment with High-Dose Trimethoprim/Sulfamethoxazole

Abstract

Specific Aims: The purpose of this study was to retrospectively evaluate sulfamethoxazole concentrations obtained in adult patients with varying degrees of renal function. The first study aim was to identify sulfamethoxazole serum concentrations obtained from patients who received high-dose trimethoprim/sulfamethoxazole. The second aim is to examine the relationship between sulfamethoxazole concentrations, trimethoprim/sulfamethoxazole doses prescribed, and subjects' estimated renal function. Methods: This institutional review board approved study examined sulfamethoxazole serum concentrations in adult patients with varying renal function. Subjects selected had recorded sulfamethoxazole blood concentrations while receiving high-dose sulfamethoxazole/trimethoprim between June 2006 and May 2012 while admitted to an academic medical center. For the first study aim, patients were grouped by renal function with estimated creatinine clearance exceeding 30 ml/min, creatinine clearance of 15 to 30 ml/min, and creatinine clearance of less than 15 ml/min. For the last group, dosing practices were described since few recommendations for this degree of renal function exist. For the first two groups, adherence to literature recommendations was evaluated. The second aim was addressed with a population pharmacokinetic analysis. A one compartment model was used with first-order elimination. Oral dosing was incorporate a separate administration compartment with first order transfer to compartment 1. Intravenous dosing was handled as a rate input into compartment 1. For patients with estimated creatinine clearance greater than 60 ml/min, all doses within the prior 48 hours were entered while those with estimated creatinine clearance less than 60 ml/min only the prior 96 hours of doses before a concentration were entered. Sulfamethoxazole concentrations were assessed in context of trimethoprim/sulfamethoxazole dose and renal function. Main Results: A total of 77 subjects who had a total of 206 sulfamethoxazole concentration(s) obtained while receiving high-dose sulfamethoxazole/trimethoprim. The sulfamethoxazole concentrations ranged from undetectable to 316.8 mcg/mL with a median value of 79.6 mcg/mL. The number of sulfamethoxazole concentrations obtained per subject ranged from 1 to 8 concentrations. The pharmacokinetic analysis of these sulfamethoxazole concentrations based on subjects’ estimated renal function and doses prescribed is in progress. Conclusion: To be determined.