title: Pharmacokinetics of N-acetylcysteine following repeated intravenous infusion in haemodialysed patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Nephrology, Ospedale Regionale di Bellinzona e Valli, 6500, Bellinzona (TI), Switzerland.
authors.forename: Davide
authors.initials: D
authors.lastname: Soldini
authors.forename: Hugo
authors.initials: H
authors.lastname: Zwahlen
authors.forename: Luca
authors.initials: L
authors.lastname: Gabutti
authors.forename: Antonio
authors.initials: A
authors.lastname: Marzo
authors.forename: Claudio
authors.initials: C
authors.lastname: Marone
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001806:Blood Urea Nitrogen; D003545:Cysteine / Q000097:blood; D004334:Drug Administration Schedule; D005100:Expectorants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005978:Glutathione / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010865:Pilot Projects; D006435:Renal Dialysis
chemical_list: D000975:Antioxidants; D005100:Expectorants; D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine