Marked alterations in dose-dependent prednisolone kinetics in women taking oral contraceptives.

Six healthy women chronically (greater than 6 months) using oral contraceptives were age- and weight-matched with female controls. Each subject received prednisolone, 0.53 and 0.14 mg/kg iv. In the subjects taking oral contraceptives there were significant decreases in total clearance, unbound clearance, and volume of distribution at steady state for total drug, and significant increases in total and unbound prednisolone t1/2 and hydrocortisone concentrations compared with control subjects at both the high and low prednisolone doses. Both the oral contraceptive group and the control group had significantly higher total clearance, volume of distribution for total drug, and unbound fraction for the high dose compared with the low dose. Data suggest that chronic low-dose contraceptive steroid use results in a marked decrease in prednisolone clearance; however, dose-dependent changes in kinetics are still observed.