Single- and multiple-dose pharmacokinetics of ethambutol and rifampicin in a tuberculosis patient with acute respiratory distress syndrome undergoing extended daily dialysis and ECMO treatment. (January 2016)

• Record Type: Journal Article
• Authors: Strunk, Ann-Kathrin; Ciesek, Sandra; Schmidt, Julius J.; Kühn, Christian; Hoeper, Marius M.; Welte, Tobias; Kielstein, Jan T.
• Is Part Of: International journal of infectious diseases. Volume 42(2016:Jan.)
• Page Start: 1
• Page End: 3
• Publication Date: 2016-01
• Subjects: Active tuberculosis -- Ethambutol -- Rifampicin -- Renal replacement therapy; Communicable diseases -- Periodicals; Communicable Diseases -- Periodicals; Communicable diseases; Periodicals; Electronic journals; 616.9
• DOI: 10.1016/j.ijid.2015.10.018
• Languages: English
• ISSNs: 1201-9712

Abstract

Highlights: Single- and multiple-dose pharmacokinetics of ethambutol (EMB) and rifampicin (RIF) in a patient requiring both ECMO and renal replacement therapy are reported for the first time. Extended dialysis eliminates EMB effectively and to a larger extent than regular intermittent haemodialysis in outpatients. Also RIF, previously reported to be non-dialysable, could be found in the spent dialysate. There was no detectable effect of the ECMO membrane on the removal of both drugs. We conclude that after an initial dose, as for patients without renal impairment (15 mg/kg/day), therapeutic drug monitoring should be used to guide EMB dosing in patients undergoing extended daily dialysis. Summary: The dosing of drugs in critically ill patients undergoing renal replacement therapy is based on limited data. We report for the first time single- and multiple-dose pharmacokinetics of ethambutol (EMB), which is cleared renally to 80%, and rifampicin (RIF), which is cleared renally to <30%, in a patient requiring both extracorporeal membrane oxygenation (ECMO) and renal replacement therapy. Extended dialysis removed a considerable amount of both EMB and RIF, with a dialyser plasma clearance ranging between 37 and 95 ml/min for EMB and between 39 and 53 ml/min for RIF. The EMB peak level (3 h after a 2-h infusion) using a dose of 1000 mg/day on the first day of treatment was 2.3 mg/l, which is in the low therapeutic range (2–5 mg/l). Doubling the dose to 2000 mg/day resulted in peak levels slightly to markedly above the recommended range. There was no detectable effect of the ECMO membrane on the removal of both drugs. After an initial dose as for patients without renal impairment (15 mg/kg/day), therapeutic drug monitoring should be used to guide EMB dosing in patients undergoing extended daily dialysis.