Effect of high-dose intravenous N-acetylcysteine on the concentration of plasma sulfur-containing amino acids.
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 microM of Cys and Met and 400 microM 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


CONCLUSIONS
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.
Hong
Sae-Yong
SY
Department of Internal Medicine, Soonchunhyang University Chunan Hospital, Chunan, Korea.
Gil
Hyo-Wook
HW
Yang
Jong-Oh
JO
Lee
Eun-Young
EY
Kim
Hyung-Kee
HK
Kim
Soo-Hyun
SH
Chung
Young-Ho
YH
Lee
Eun-Mi
EM
Hwang
Soo-Kyung
SK
D000111:Acetylcysteine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000596:Amino Acids / Q000097:blood* / Q000737:chemistry; D005978:Glutathione / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D017382:Reactive Oxygen Species; D013455:Sulfur / Q000097:blood*
D000596:Amino Acids; D017382:Reactive Oxygen Species; D013455:Sulfur; D005978:Glutathione; D000111:Acetylcysteine