title: The effect of hemodialysis on cycloserine, ethionamide, para-aminosalicylate, and clofazimine.
abstract: OBJECTIVE
  Determine hemodialysis clearances of the second-line antitubercular drugs cycloserine (CS), ethionamide (ETA), para-aminosalicylate (PAS), and clofazimine (CFZ).
  
  
  METHODS
  Open-label, pharmacokinetic study
  
  
  METHODS
  Outpatient long-term hemodialysis unit
  
  
  METHODS
  Eight long-term hemodialysis patients Interventions: Single oral doses of CS, 500 mg, ETA, 500 mg, PAS, 4,000 mg, and CFZ, 200 mg, were given 2 h (4 h for PAS) prior to hemodialysis (median blood flow rate, 400 mL/min; median dialysate flow rate, 600 mL/min; median hemodialysis time, 3.5 h).
  
  
  RESULTS
  Arterial and venous serum samples were collected at the beginning and end of hemodialysis, and hourly during hemodialysis. Dialysate fluid was collected for the duration of hemodialysis. All samples were assayed for drug concentrations using validated high-performance liquid chromatography (for ETA and PAS), capillary electrophoresis (for CS), and colorimetry (for CFZ). Dialysate samples were analyzed for acetyl-PAS. Median recoveries of drug in dialysate were 56% (CS), 2.1% (ETA), 6.3% (PAS parent compound), and 0% (CFZ) of the doses administered. Acetyl-PAS was dialyzed to a greater extent than its parent compound. Median hemodialysis clearances calculated by dividing the amount recovered in dialysate by the serum area under the curve during dialysis were 189 (CS), 58 (ETA), 206 (PAS), and 0 (CFZ) mL/min.
  
  
  CONCLUSIONS
  ETA, CFZ, and PAS were not significantly dialyzed. CS is significantly removed by hemodialysis and should be dosed after hemodialysis.
authors.affiliation: Infectious Disease Pharmacokinetics Laboratory , National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Malone
authors.forename: D N
authors.initials: DN
authors.lastname: Fish
authors.forename: D M
authors.initials: DM
authors.lastname: Spiegel
authors.forename: J M
authors.initials: JM
authors.lastname: Childs
authors.forename: C A
authors.initials: CA
authors.lastname: Peloquin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D010131:Aminosalicylic Acid / Q000493:pharmacokinetics*; D000995:Antitubercular Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D002991:Clofazimine / Q000493:pharmacokinetics*; D003523:Cycloserine / Q000493:pharmacokinetics*; D005000:Ethionamide / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008875:Middle Aged; D006435:Renal Dialysis
chemical_list: D000995:Antitubercular Agents; D010131:Aminosalicylic Acid; D003523:Cycloserine; D002991:Clofazimine; D005000:Ethionamide