Pharmacokinetics of N-acetylcysteine following repeated intravenous infusion in haemodialysed patients

• Published in: European journal of clinical pharmacology 2005-02, Vol.60 (12), p.859-864
• Main Authors: SOLDINI, Davide, ZWAHLEN, Hugo, GABUTTI, Luca, MARZO, Antonio, MARONE, Claudio
• Format: Article
• Language: English
• Subjects: Acetylcysteine - administration & dosage; Acetylcysteine - pharmacokinetics; Aged; Antioxidants - administration & dosage; Antioxidants - pharmacokinetics; Area Under Curve; Biological and medical sciences; Blood Urea Nitrogen; Cysteine - blood; Drug Administration Schedule; Expectorants - administration & dosage; Expectorants - pharmacokinetics; Female; Glutathione - blood; Humans; Infusions, Intravenous; Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - therapy; Male; Medical sciences; Metabolic Clearance Rate; Middle Aged; Pharmacology. Drug treatments; Pilot Projects; Renal Dialysis
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-004-0850-0

N-acetylcysteine (NAC) is a mucolytic agent with anti-oxidant properties. It might have potential positive effects in renal patients and, therefore, its pharmacokinetics and safety in haemodialysis was investigated. Twelve dialysis patients received 2 g NAC (10 ml NAC 20% solution i.v.) mixed with 500 ml saline during the first 3 h of the session for six dialysis sessions. A bolus of heparin was injected intravenously as LWH-heparin. In six patients, one session was repeated with NAC mixed with heparin and infused through the heparin pump. Baseline NAC was on average 454 ng ml(-1); its concentration increased to 9,253 ng ml(-1) at the second infusion and attained a steady state between 14,000 ng ml(-1) and 17,000 ng ml(-1) at the fourth dose. We observed a C (max) of 53,458 ng ml(-1) with a t (max) of 3.0 h. Plasma clearance was 1.25 l h(-1) and dialytic clearance 5.52 l h(-1). No side effects were observed. In the case of repeated doses, the NAC pre-dose concentration after repeated infusion of 2 g of the drug during the first 3 h of a dialysis session reached the steady state at the fourth infusion, without further accumulation. The dialytic clearance is effective, the total body clearance being reduced to 1.25 l h(-1). In dialysis patients, 2 g NAC given intravenously over 3 h is a safe dosage, with no short-term side effects.