The effect of hemodialysis on isoniazid, rifampin, pyrazinamide, and ethambutol.

This study examines hemodialysis clearances of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Seven chronic hemodialysis patients were studied. Six were given single oral doses (INH 300 mg, RIF 600 mg, PZA 1000 mg, and EMB 25 mg/kg) 2 h before hemodialysis (Cobe Centrysystem 3 hemodialysis machine; Fresenius F80B dialyzer; median blood flow rate 400 ml/min; dialysate flow rate 600 ml/min; median hemodialysis time 3.5 h). The seventh subject, being treated for tuberculosis (TB), was studied with his usual regimen. Arterial and venous serum samples were collected at the beginning and end of hemodialysis, and hourly during hemodialysis. Dialysate was collected for the duration of hemodialysis. All samples were assayed for drug concentrations using high-performance liquid chromatography (HPLC) (INH, RIF) and gas chromatography/mass spectrometry (GC/MS) (PZA, EMB) methods. Median recoveries of drug in dialysate were 9% (INH), 4% (RIF), 45% (PZA), and 2% (EMB) of the doses administered. Median hemodialysis clearances calculated by dividing the amount recovered in dialysate by the serum area under the curve during hemodialysis were 124 (INH), 40 (RIF), 270 (PZA), and 46 (EMB) ml/min. INH, RIF, and EMB were not significantly removed by hemodialysis. PZA is significantly dialyzed and should be dosed after hemodialysis.