The effect of hemodialysis on cycloserine, ethionamide, para-aminosalicylate, and clofazimine.
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.
Malone
R S
RS
Infectious Disease Pharmacokinetics Laboratory , National Jewish Medical and Research Center, Denver, CO 80206, USA.
Fish
D N
DN
Spiegel
D M
DM
Childs
J M
JM
Peloquin
C A
CA
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
D000995:Antitubercular Agents; D010131:Aminosalicylic Acid; D003523:Cycloserine; D002991:Clofazimine; D005000:Ethionamide