THERAPEUTIC SUBSTANCES

1. In animals and in cultured neurons, L-carnitine and acetyl-L-carnitine (ALCAR) have been shown to counteract some of the toxic effects of ammonia. In order to detect similar properties in humans, we studied neuronal function after ALCAR administration in cirrhotics with hepatic encephalopathy (HE). 2. Eighteen cirrhotic patients with persistent HE and hyperammonaemia were investigated in the present study and six subjects with a prior transient ischaemic attack were used as controls. 3. The prominent positive component that occurs approximately 100 msec after the pattern reversal (P100) latencies of visual-evoked potentials were used to evaluate neuronal function. At first, the P100 latency was measured in six cirrhotic patients with HE and in the six controls before the administration of 0.5 g ALCAR in 50 mL isotonic saline (infusion rate 10 mL/min) and 15, 30, 60 and 90 min later. 4. A significant reduction in P100 latencies was identified 30 min after ALCAR infusion in HE patients, whereas no differences were observed in controls. 5. Thereafter, the P100 latency was evaluated in the 12 other cirrhotic patients with HE only before and 30 min after ALCAR infusion. The mean of the P100 latencies measured in these subjects was significantly shorter after ALCAR infusion compared with values obtained before ALCAR administration (mean (+/-SD) 130.78 +/- 5.50 vs 136.08 +/- 6.45 msec, respectively; P = 0.0013). 6. The present study suggests that a single intravenous dose of ALCAR may transiently improve neuronal function in cirrhotic patients with persistent HE and hyperammonaemia.