Abstract | BACKGROUND AND OBJECTIVES: DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Twenty-four ESRD patients were randomly assigned to receive 600 or 1200 mg of sustained-release NAC orally every 12 hours for 14 days. Seven healthy control subjects received NAC 600 mg in the same manner. Blood samples were obtained on days 1 and 15 for determination of NAC pharmacokinetics and pharmacodynamics. RESULTS: Significant dose-related increases in NAC plasma concentrations were observed in ESRD patients with no change in total clearance; a doubling of the dose resulted in a 2-fold increase in NAC area under the plasma concentration-time curve (AUC). However, NAC clearance was reduced by 90% in ESRD, leading to a 7-fold larger AUC and 13-fold longer half-life compared with healthy control subjects. NAC administration resulted in a significant reduction in total homocysteine plasma concentrations in ESRD and healthy subjects, but had no effect on several other oxidative stress markers. CONCLUSIONS: These findings indicate that the total clearance of oral NAC is significantly reduced in ESRD patients, leading to marked increases in systemic exposure, and suggest that NAC may have a limited role in the chronic treatment of oxidative stress-related illness.
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Authors | Thomas D Nolin, Rosemary Ouseph, Jonathan Himmelfarb, M Elizabeth McMenamin, Richard A Ward |
Journal | Clinical journal of the American Society of Nephrology : CJASN
(Clin J Am Soc Nephrol)
Vol. 5
Issue 9
Pg. 1588-94
(Sep 2010)
ISSN: 1555-905X [Electronic] United States |
PMID | 20538838
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
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Chemical References |
- Antioxidants
- Biomarkers
- Delayed-Action Preparations
- Homocysteine
- Acetylcysteine
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Topics |
- Acetylcysteine
(administration & dosage, blood, pharmacokinetics)
- Administration, Oral
- Adult
- Antioxidants
(administration & dosage, pharmacokinetics)
- Area Under Curve
- Biomarkers
(blood)
- Delayed-Action Preparations
- Down-Regulation
- Female
- Half-Life
- Homocysteine
(blood)
- Humans
- Kidney Failure, Chronic
(blood, drug therapy)
- Male
- Metabolic Clearance Rate
- Middle Aged
- Oxidative Stress
(drug effects)
- Prospective Studies
- Treatment Outcome
- United States
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