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Clinical Investigations: ANTIBIOTICS |

The Effect of Hemodialysis on Cycloserine, Ethionamide, Para-Aminosalicylate, and Clofazimine*

Rebecca S. Malone, PharmD; Douglas N. Fish, PharmD; David M. Spiegel, MD; James M. Childs, BS; Charles A. Peloquin, PharmD
Author and Funding Information

*From the Infectious Disease Pharmacokinetics Laboratory (Drs. Malone and Peloquin, and Mr. Childs), National Jewish Medical and Research Center, Denver, CO; and the School of Pharmacy (Dr. Fish) and the School of Medicine (Dr. Spiegel), University of Colorado Health Sciences Center, Denver, CO.

Correspondence to: Charles A. Peloquin, PharmD, Infectious Disease Pharmacokinetics Laboratory, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206; e-mail: Peloquinc@njc.org



Chest. 1999;116(4):984-990. doi:10.1378/chest.116.4.984
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Published online

Study objectives: Determine hemodialysis clearances of the second-line antitubercular drugs cycloserine (CS), ethionamide (ETA), para-aminosalicylate (PAS), and clofazimine (CFZ).

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 (median blood flow rate, 400 mL/min; median dialysate flow rate, 600 mL/min; median 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. 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.


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