Improvement of statin-associated myotoxicity by L-carnitine.

Although statins represent the mainstay therapy for the treatment of hypercholesterolemia and have a positive tolerability and safety profile, the occurrence of statinassociated myopathy, an accepted class effect of these drugs, may bemore common than originally thought. In this regard, a recent paper by Phillips and collegues on the myotoxic effect of statin has been followed by a number of interesting letters and authors’ responses addressing several issues of statin myotoxicity [1,2]. Among them, Toma reasoned that L-carnitine (LC) treatment might have a favorable impact on the incidence of statin-associated therapy [2]. We have recently completed a study in young rodents treated with myotoxic doses of simvastatin, a useful model for statin myotoxicity studies [3], in combination or not with LC and our results strengthen Toma’s proposal in addressing the preventive or therapeutic effect of LC on statin-associated myopathy in human clinical trials. Indeed, our study shows that, at the highest dose of simvastatin, creatine kinase (CK) plasma levels were significantly elevated in treated animals compared with controls and that carnitine coadministration efficiently counteracted plasma CK levels in the former group (Table 1). Statin treatment at the two highest doses also caused a significant elevation of glutamic oxalacetate transaminase (GOT) and glutamic pyruvate transaminase (GPT), which may reflect both hepatic and muscle insult. LC administration did not lead to a significant correction of these two enzymatic indices in statin-treated groups, although, at the highest dose of simvastatin, LC seems to oppose GOT and GPT elevations (Table 1). The beneficial effect of carnitine administration in the simvastatin-treated animals does not seem to be linked to an alteration of the pharmacokinetic properties of the statin, since the cholesterollowering effect observed at the highest dose of simvastatin was not affected by carnitine (Table 1). Statin-treated animals were also treadmill-tested at a constant 15 angle and a speed of 10 m min. As expected, their walking capacity was severely impaired at the highest statin dose (90% of rats fell more than three times over a period of 5 min walking) compared with controls (no fall over a period of 5 min walking). A marked improvement by adding carnitine to statin treatment was observed (60% of rats fell more than three times over a period of 5 min walking). Themajority of the specificmyotoxic actions described in the literature seem to indicate that muscle membrane represents a common pathogenic target of statins’ mode of action [4]. Since several cellular functions rely on the integrity of biological membranes (i.e. ionic homeostasis, signal transduction, com-