Pharmacokinetics and effects of inhaled fluticasone propionate on adrenal function in asthmatic patients: Dose-ranging and comparison with oral prednisone

The pharmacokinetics of fluticasone propionate (FP) and the effects on adrenal function of 28 days treatment with placebo, prednisone 10 mg/day, 220, 440, 660, or 880 μg BID doses of FP were assessed in 118 asthmatic patients. There was considerable variability in systemic absorption as evidenced by FP area under the plasma concentration versus time curves (AUC) but mean AUC values were proportional to dose: 335, 784, 1064 and 1366 ng.hr/L, respectively. Patients underwent a 6-hour cosyntropin infusion before and after 28 days of treatment. Plasma cortisol was measured over 0 to 12 hr and at 24 hr; urinary cortisol excretion was measured over 24 hr. The cortisol AUCs were calculated and fitted with a pharmacodynamic model which yielded the Cortisol Influx Rate. Doses of 220 μg FP showed responses similar to placebo. Diminished adrenal responses occurred only when the AUC of FP exceeded 1000 ng·hr/L and then only in a small percentage of patients: 10% at 440, 16% at 660 and 12% at 880 pg FP BID. In contrast, responses were impaired in 29% patients on prednisone. Inhaled FP sometimes produces impairment of adrenal response to stimulation, but to a degree less than 10 mg/day prednisone.