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.

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.