The effect of hemodialysis on cycloserine, ethionamide, para-aminosalicylate, and clofazimine

Study objectives: Determine hemodialysis clearances of the second-line anti tubercular drugs cycloserine (CS), ethionamide (ETA), para-aminosalicylate (PAS), and clofazimine (CPZ). Design: Open-label, pharmacokinetic study Setting: Outpatient long-term hemodialysis unit Participants: 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 (media n blood flow rate, 400 mL/min; median dialysate flow rate, 600 mL/min; medi an hemodialysis time, 3.5 h), Measurements and results: Arterial and venous serum samples were collected at the beginning and end of hemodialysis, and hourly during hemodialysis. D ialysate fluid was collected for the duration of hemodialysis. All samples were assayed for drug concentrations using validated high-performance liqui d chromatography (for ETA and PAS), capillary electrophoresis (for CS), and colorimetry (for CFZ). Dialysate samples were analyzed for acetyl-PAS. Med ian recoveries of drug in dialysate were 56% (CS), 2.1% (ETA), 6.3% (PAS pa rent compound), and 0% (CFZ) of the closes administered. Acetyl-PAS was dia lyzed to a greater extent than its parent compound. Median hemodialysis cle arances calculated by dividing the amount recovered in dialysate by the ser um 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 signi ficantly removed by hemodialysis and should be dosed after hemodialysis.