Effect of liver cirrhosis on the systemic availability of naltrexone in humans

Background/Aims: Naltrexone is a competitive opiate antagonist with high hepatic extraction. It is used for detoxification treatment for heroin addicts and has been proposed as a possible treatment of pruritus in cholestasis. Such patients are likely to have impaired liver function, underscoring the need to understand the pharmacokinetic behavior of naltrexone in liver disease. These studies were undertaken to evaluate the effect of liver cirrhosis on the plasma time-course of naltrexone. Methods: A total of 18 patients were investigated: seven migraine patients with normal liver function regarded as controls and 11 patients with liver cirrhosis (six with decompensated disease and five with preserved liver function). A bolus of 100 mg of naltrexone was administered orally in the morning, after an overnight fast. Blood samples were taken in basal conditions and at fixed intervals, up to 24 h after administration. Serum levels of naltrexone and of its major active metabolite, 6β-naltrexol, were assayed by reversed-phase HPLC analysis. Results: In control subjects, circulating concentrations of naltrexone were always much lower than those of 6β-naltrexol (area under the curve: naltrexone, 200±97 ng/ml×24 h; 6β-naltrexol, 2467±730 ng/ml×24 h, p