BIOAVAILABILITY OF ORAL CYCLOSPORINE IN HEALTHY MEXICAN VOLUNTEERS - EVIDENCE FOR INTERETHNIC VARIABILITY

The existence of population variations in cyclosporine pharmacokinetic s could be expected, as this drug, similar to nifedipine, is biotransf ormed by cytochrome P-450 subfamily 3A4, and the existence of intereth nic variability in nifedipine disposition has been demonstrated previo usly. The bioavailability of oral cyclosporine rr as studied in 23 hea lthy Mexican volunteers receiving 7.5-mg/kg doses of cyclosporine. Blo od samples were drawn over 24 hours, and concentration of cyclosporine in tt hole blood rt as determined by a radioimmunoassay using monoclo nal antibodies specific for the unchanged drug. The bioavailability of cyclosporine exhibited wide interindividual variability. Maximum conc entration (C-max) ranged from 528 ng/mL to 2,689 ng/mL, area under the concentration-time curve (AUG) ranged from 6,550 ng.hr/mL to 18,562 n g.hr/mL, and time to reach C-max (t(max)) ranged from 1 to 8 hours. Ha lf-life (t(1/2)) exhibited less important variations, ranging from 4.4 to 9.1 hours. The bioavailability of oral cyclosporine in Mexicans wa s higher than that reported for white populations under similar condit ions. The present results suggest the existence of interethnic variabi lity in the pharmacokinetics of cyclosporine, as is the case with nife dipine.