Pharmacokinetics of N‐acetylcysteine are altered in patients with chronic liver disease

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Abstract
Background: The threshold plasma paracetamol concentration at which N‐acetylcysteine (NAC) treatment is recommended to treat paracetamol poisoning in a patient with induced liver enzymes (for example, with chronic liver disease or taking anticonvulsant drugs) is 50% lower than in a patient without induced liver enzymes. More patients with chronic liver disease might therefore be expected to be exposed to NAC treatment than previously. In addition, there is increasing use of NAC in patients with chronic liver disease for multiorgan failure or hepatorenal syndrome. Little is known of NAC's pharmacokinetic properties in patients with cirrhosis. Aim: The aim was to determine if the pharmacokinetics 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 patients with biopsy‐proven cirrhosis (Child's grade; 1 A, 4 B, 4 C; aetiology: 7 alcohol‐related, 1 primary biliary cirrhosis, 1 secondary biliary stenosis) and six healthy matched controls. Venous blood was taken at 20, 40, 60 and 90 min then at 2, 3, 4, 6, 8 and 10 h after NAC administration. Serum NAC was estimated by HPLC. The data were normalized to a standard body weight of 70 kg. Results: The area under the serum 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 chronic 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 untoward anaphylactoid reactions is necessary in cirrhotics as they may have higher plasma NAC concentrations. Further studies to determine the optimum dosage regimen in such patients are required.