Effect of high-dose intravenous N-acetylcysteine on the concentration of plasma sulfur-containing amino acids
- 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 µM of Cys and Met and 400 µM 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.
- All Author(s)
- S. Y. Hong
; H. W. Gil
; J. O. Yang
; E. Y. Lee
; H. K. Kim
; S. H. Kim
; Y. H. Chung
; E. M. Lee
; S. K. Hwang
- Issued Date
- 2005
- Type
- Article
- Keyword
- Acetylcysteine; Reactive oxygen species; Amino acids; Sulfur
- Publisher
- 대한내과학회
Korean Association of Internal Medicine
- ISSN
- 1226-3303
; 2005-6648
- Citation Title
- The Korean journal of internal medicine
- Citation Volume
- 20
- Citation Number
- 3
- Citation Start Page
- 217
- Citation End Page
- 223
- Language(ISO)
- eng
- DOI
- 10.3904/kjim.2005.20.3.217
- URI
- http://schca-ir.schmc.ac.kr/handle/2022.oak/3234
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