Korean J Intern Med.
2005 Sep;20(3):217-223. 10.3904/kjim.2005.20.3.217.
Effect of High-Dose Intravenous N-acetylcysteine on the Concentration of Plasma Sulfur-Containing Amino Acids
- Affiliations
-
- 1Department of Internal Medicine, Soonchunhyang University Chunan Hospital, Chunan, Korea. hwgil@schch.co.kr
- 2Department of Clinical Pharmacology, Soonchunhyang University Chunan Hospital, Chunan, Korea.
- 3Proteome Analysis Team, Korea Basic Science Institute, Daejeon, Korea.
- KMID: 1782233
- DOI: http://doi.org/10.3904/kjim.2005.20.3.217
Abstract
- BACKGROUND
The purpose of this study was to determine the adequate loading and maintenance doses of N-acetylcyseteine (NAC) for patients suffering from acute ROS-induced injury. METHODS: Concentrations of extra cellular NAC, cysteine (Cys), cystine (Cyst2), and methionine (Met) were measured in vitro, at which more than 50% of the intracellular ROS raised by paraquat were suppressed using Swiss 3T3 fibroblasts. An in vivo pharmacokinetic study followed on a healthy subject to determine the proper loading and maintenance doses of reduced NAC following intravenous administration of 25 mg/kg NAC. RESULTS: In vivo, NAC suppressed ROS in a dose dependant manner. 10 mM of NAC suppressed about 50% of ROS, and was comparable to 10 micro M of Cys and Met and 400 micro M of Cys2. In vitro, the elimination of half-life was achieved at 2.88+/-1.14 h for NAC and at 3.68+/-1.84 h for total NAC. The body clearances were 1.23+/-0.77 L h (-1) kg (-1) and 0.56+/-0.27 L h (-1) kg (-1) and the volumes of distribution were 3.07+/-0.10 L kg (-1) and 3.00+/-0.11 L kg (-1), respectively. The loading and maintenance NAC doses used to reach the target concentration of 10 mM, were 5010 mg. kg (-1) and 2250 mg min (-1) kg (-1), respectively. CONCLUSION: NAC provides an antioxidant effect on ROS produced by paraquat in vivo. However, in vitro, our results showed that the intravenous NAC dose could not be estimated from NAC plasma concentration or its metabolites.
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