title: 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.
abstract: 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 (3h after a 2-h infusion) using a dose of 1000 mg/day on the first day of treatment was 2.3mg/l, which is in the low therapeutic range (2-5mg/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.
authors.affiliation: Department of Nephrology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Electronic address: ann-kathrin.strunk@gmx.net.
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Strunk
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ciesek
authors.affiliation: Department of Nephrology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Julius J
authors.initials: JJ
authors.lastname: Schmidt
authors.affiliation: Department of Cardiothoracic Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kühn
authors.affiliation: Department of Pulmonary Medicine, German Centre for Lung Research, Hannover Medical School, Hannover, Germany.
authors.forename: Marius M
authors.initials: MM
authors.lastname: Hoeper
authors.affiliation: Department of Pulmonary Medicine, German Centre for Lung Research, Hannover Medical School, Hannover, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.affiliation: Department of Nephrology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Jan T
authors.initials: JT
authors.lastname: Kielstein
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000493:pharmacokinetics*; D004977:Ethambutol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015199:Extracorporeal Membrane Oxygenation; D006801:Humans; D008297:Male; D006435:Renal Dialysis / Q000379:methods; D012128:Respiratory Distress Syndrome / Q000628:therapy*; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D004977:Ethambutol; D012293:Rifampin
keywords: Active tuberculosis; Ethambutol; Renal replacement therapy; Rifampicin