Tolerability of fibric acids, comparative data and biochemical bases

Fibric acids are an established class of drugs for the treatment of hyperlipoproteinaemias. Although they have been in use for 30 years or longer, some doubts remain as to their relative tolerability, both as a class and as single agents. Some side effects, e.g. lithogenicity, may be related to their mode of action, while others, e.g. the acute muscular syndrome, may be linked to the spatial conformation of the molecule. These disadvantages should, however, be weighed against the additional, potentially therapeutic properties shown by these compounds. In particular, effects on maturity onset diabetes and hyperuricaemia, as well as a very interesting fibrinolysic potential, have been described for some of them. A painstaking comparative analysis of the major literature data pertaining to the clinical toxicological profile of these agents allow to conclude that, while belonging to a chemical class, fibric acids show dramatic differences from one another, in terms of side effects and of additional pharmacodynamic activities. Moreover, in the case of lithogenicity for example, considerable differences exist between normo- and hyperlipidaemic subjects. Overall, newer molecules of more sophisticated design have a significantly improved tolerability profilevs the old clofibrate.