Bioavailability of Oral Cyclosporine in Healthy Mexican Volunteers: Evidence for Interethnic Variability

Abstract

The existence of population variations in cyclosporine pharmacokinetics could be expected, as this drug, similar to nifedipine, is biotransformed by cytochrome P‐450 subfamily 3A4, and the existence of interethnic variability in nifedipine disposition has been demonstrated previously. The bioavailability of oral cyclosporine was studied in 23 healthy Mexican volunteers receiving 7.5‐mg/kg doses of cyclosporine. Blood samples were drawn over 24 hours, and concentration of cyclosporine in whole blood was determined by a radioimmunoassay using monoclonal antibodies specific for the unchanged drug. The bioavailability of cyclosporine exhibited wide interindividual variability. Maximum concentration (C_max) ranged from 528 ng/mL to 2,689 ng/mL, area under the concentration—time curve (AUC) ranged from 6,550 ng · hr/mL to 18,562 ng · hr/mL, and time to reach C_max (t_max) ranged from 1 to 8 hours. Half‐life (t_1/2) exhibited less important variations, ranging from 4.4 to 9.1 hours. The bioavailability of oral cyclosporine in Mexicans was higher than that reported for white populations under similar conditions. The present results suggest the existence of interethnic variability in the pharmacokinetics of cyclosporine, as is the case with nifedipine.