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

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.Conclusion 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.The study was conducted in accordance with the guidelines for Good Clinical Practice and all current Swiss laws concerning clinical research. The protocol was approved by the Ethics Committee of the Canton Ticino, Switzerland.