1999). Renal clearance has been reported at 0.190–0.211 L/h per kg; however, up to 70% of the total body clearance is nonrenal. With oral administration, reduced NAC has a terminal half-life of 6.25 h. It is believed to be rapidly metabolized and incorporated onto proteins. After oral ingestion of 200 mg NAC,

the free thiol is largely undetectable, and only low levels of oxidized NAC are detectable for several hours after administration (Cotgreave and Moldeus 1987). The data also indicate that the drug is less than 5% bioavailable from the oral formulation. Further pharmacokinetic data suggest that the drug itself does not Inhibitors,research,lifescience,medical accumulate in the body, but rather in its oxidized forms and in reduced and oxidized metabolites (Holdiness 1991; Watson and McKinney 1991). Pharmacokinetic information is controversial regarding Inhibitors,research,lifescience,medical NAC ability to cross placenta or being Ki16425 supplier excreted into breast milk. NAC in the Ames test is negative; however, animal studies on embryotoxicity

are equivocal (Ziment 1988). In addition, studies in pregnant women are inadequate. Therefore, NAC should be used with caution during pregnancy, and only if clearly indicated. Its major excretory product is inorganic sulfate. NAC is generally safe and well tolerated even at high doses. Most frequently reported side effects Inhibitors,research,lifescience,medical are nausea, vomiting, and diarrhea. Therefore, oral administration is contraindicated in persons with active peptic ulcer (Ziment 1988). Biochemical and hematological adverse effects are observed, but are not clinically relevant. Drug interactions of clinical significance have been observed with paracetamol, GSH, and Inhibitors,research,lifescience,medical anticancer agents (Holdiness 1991). Infrequently, anaphylactic reactions due to histamine release occur and can consist of rash, pruritis, angioedema, bronchospasm, tachycardia, and changes in blood pressure. In rare circumstances, intravenous administration of NAC can lead to an allergic reaction generally Inhibitors,research,lifescience,medical in the form of rash or angioedema.

In addition, as with any antioxidant nutrient, NAC at therapeutic doses (even as low as 1.2 g daily) has the potential to have pro-oxidant activity and therefore it is not recommended in the absence of a significant confirmed oxidative stress (Ziment 1988). NAC strongly potentiates the effect of nitroglycerin and related medications, and caution should be used Phosphoprotein phosphatase in patients receiving these agents in whom it may cause hypotension (Atkuri et al. 2007). Conclusions NAC has a broad spectrum of actions and possible applications across multiple conditions and systems. As a drug, NAC represents perhaps the ideal xenobiotic, capable of directly entering endogenous biochemical processes as a result of its own metabolism. In addition, NAC may cross the BBB. In neurological diseases, there is a potential to explore doses and duration of treatment with NAC to achieve cytoprotection. Conflict of Interest None declared.