Effect of peritoneal dialysis on plasma and peritoneal fluid concentrations of isoniazid, pyrazinamide, and rifampin.
OBJECTIVE
This study was performed to elucidate the pharmacokinetic profiles of antimycobacterial regimens for peritoneal dialysis patients.


METHODS
Nine patients on maintenance continuous ambulatory peritoneal dialysis (CAPD) were included in this study.


METHODS
After administering a conventional oral dose of antituberculosis medications, we measured plasma and peritoneal fluid concentrations of isoniazid by fluorometry, and rifampin and pyrazinamide by high performance liquid chromatography. The assay data were subjected to pharmacokinetic analysis.


RESULTS
Average peak plasma concentrations of isoniazid, rifampin, and pyrazinamide were 3.3 mg/L, 6.5 mg/L, and 30.9 mg/L, respectively, all of which much exceed the minimum inhibitory concentration (MIC) for Mycobacterium tuberculosis. Peritoneal fluid concentrations of isoniazid and pyrazinamide were maintained well above the MICs for M. tuberculosis; however, peritoneal fluid concentration of rifampin was below the therapeutic range most of the time.


CONCLUSIONS
For the treatment of systemic or pulmonary tuberculosis in CAPD patients, no dose adjustments are required for isoniazid, rifampin, or pyrazinamide. On the contrary, for the treatment of tuberculous peritonitis, oral rifampin therapy is not expected to be effective because of its low peritoneal fluid concentration.
Ahn
Curie
C
Department of Nephrology, College of Medicine, Seoul National University, Seoul, Korea.
Oh
Kook-Hwan
KH
Kim
Kiwon
K
Lee
Kyung Yi
KY
Lee
Jung Geon
JG
Oh
Myung Don
MD
Kim
Yonsu
Y
Han
Jin Suk
JS
Kim
Suhnggwon
S
Lee
Jung Sang
JS
Jang
In-Jin
IJ
Shin
Sang-Goo
SG
D000328:Adult; D000995:Antitubercular Agents / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D001202:Ascitic Fluid / Q000737:chemistry*; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000379:methods*; D011718:Pyrazinamide / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D012293:Rifampin / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*
D000995:Antitubercular Agents; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin