[Clinical pharmacology of calcium inhibitors]

The pharmacokinetics of the commercially available calcium antagonists, diltiazem (Tildiem), nifedipine (Adalate), perhexiline (Pexid), and verapamil (Isoptine) are well known; the pharmacokinetics of bepridil (Cordium) need further study. The properties of nicarpidine, a molecule currently being tested, will also be described. These products are well absorbed from the gastrointestinal tract but undergo variable degrees of transformation during the first passage through the liver. The bioavailabilities of bepridil, diltiazem and nifedipine are of the order of 40 to 60%; those of verapamil and nicarpidine are lower, 10-20% and 15-30%, respectively. The rates of absorption vary according to the derivatives and galenic preparations; in general, they are rapid; peak plasma concentrations are usually obtained one to four hours after administration. Protein binding is high but does not interfere in the distribution; the volumes of distribution of bepridil, diltiazem and verapamil are large (4-5 l/kg); those of nifedipine and nicardipine are smaller (l l/kg). The halflives of diltiazem, nifedipine, nicardipine and verapamil are short (1 to 5 hours); those of bepridil and perhexiline are longer (2 to 3 days). The main method of elimination is by hepatic transformation with high plasma clearance rates: diltiazem and verapamil have pharmacologically active derivatives whose contributions to the overall activities of the drugs are not fully understood. Physiopathological changes of the pharmacokinetic properties of diltiazem and verapamil (elderly patients, hepatic failure) have been described.