PHARMACOKINETICS OF N-ACETYLCYSTEINE ARE ALTERED IN PATIENTS WITH CHRONIC LIVER-DISEASE

Background: The threshold plasma paracetamol concentration at which N- acetylcysteine (NAC) treatment is recommended to treat paracetamol poi soning in a patient with induced liver enzymes (for example, with chro nic liver disease or taking anticonvulsant drugs) is 50% lower than in a patient without induced liver enzymes, More patients with chronic l iver disease might therefore be expected to be exposed to NAC treatmen t than previously. In addition, there is increasing use of NAC in pati ents with chronic liver disease for multiorgan failure or hepatorenal syndrome. Little is known of NAC's pharmacokinetic properties in patie nts with cirrhosis. Aim: The aim was to determine if the pharmacokinet ics of NAC are altered by chronic liver disease. Subjects and methods: NAC was given intravenously in a dose of 600 mg over 3 min to nine pa tients with biopsy-proven cirrhosis (Child's grade; 1 A, 4 B, 4 C; aet iology: 7 alcohol-related, 1 primary biliary cirrhosis, 1 secondary bi liary stenosis) and six healthy matched controls, Venous blood was tak en at 20, 40, 60 and 90 min then at 2, 3, 4, 6, 8 and 10 h after NAC a dministration. Serum NAC was estimated by HPLC, The data were normaliz ed to a standard body weight of 70 kg. Results: The area under the ser um concentration-time curve was increased (152.34 mg/L.h +/- 50.38 s.d .) in cirrhotics compared with normal controls (93.86 mg/L.h +/- 9.60 s.d.) (P < 0.05). The clearance of NAC was reduced in patients with ch ronic liver disease (4.52 L/h +/- 1.87 s.d.) compared with controls (6 .47 L/h +/- 0.78; P < 0.01). Conclusions: Increased Vigilance for unto ward anaphylactoid reactions is necessary in cirrhotics as they may ha ve higher plasma NAC concentrations. Further studies to determine the optimum dosage regimen in such patients are required.