Pharmacokinetics of trimethoprim/sulfametrole in critically ill patients on continuous renal replacement therapy

Objectives: We investigated the effect of continuous renal replacement therapy (CRRT) on the pharmacokinetics of trimethoprim and sulfametrole. Patients and methods: We enrolled critically ill adults undergoing CRRT and critically ill adults with normal or slightly impaired renal function (plasma creatinine concentration <1.5mg/dL, control group). All patients received trimethoprim/sulfametrole at standard doses. Pharmacokinetics were determined after the first dose and at steady-state. In addition, a population pharmacokinetic model using plasma data was built. We also assessed the renal clearance (CLR) and the extracorporeal clearance in patients undergoing CRRT. Results: Twelve patients were enrolled in the CRRT group and 12 patients in the control group. There was no statistically significant difference in trimethoprim pharmacokinetics between the two groups. In patients on CRRT, total plasma clearance (CLtot) and V of sulfametrole were significantly higher than in the control group. However, sulfametrole exposure was not significantly altered during CRRT. The population pharmacokinetic analysis indicated that neither CRRT intensity nor residual diuresis were significant covariates on trimethoprim or sulfametrole CL. Median CL by continuous venovenous haemofiltration accounted for about one-third of CLtot of trimethoprim and for about one-half of CLtot of sulfametrole. In patients on CRRT, CLR of trimethoprim and sulfametrole were <5% of CLtot. Conclusions: During CRRT, standard doses of trimethoprim/sulfametrole appear to be adequate.