Once-daily dual-release hydrocortisone was associated with a more
circadian-based serum cortisol profile compared with the thrice-daily dose
tablets in patients with adrenal insufficiency.
Researchers compared the pharmacokinetics and metabolic outcome of
once-daily and thrice-daily hydrocortisone tablets in an open, randomized,
two-period, 12-week crossover, multicenter study conducted at five university
hospitals. The trial included a 24-week extension.
Sixty-four adults with primary adrenal insufficiency were included in
the study; 11 had concomitant
diabetes and the mean age was 47 years.
Dual-release tablets (20 mg and 5 mg) were administered orally once
daily in the morning during fasting. The reference drug was 10 mg
hydrocortisone thrice daily.
The once-daily dose provided sustained serum
cortisol profile zero to 4 hours after morning intake and
reduced late afternoon and 24-hour cortisol exposure vs. the thrice-daily dose,
the researchers wrote. Additionally, at 12 weeks, the once-daily tablets were
associated with decreases in mean weight (P=.005), systolic blood
pressure (P=.0001) and diastolic BP (P=.03), as well as glycated
hemoglobin (P=.0006), compared with the thrice-daily dose.
Patients with concomitant diabetes experienced a 0.6% reduction in
glycated hemoglobin after the once-daily dose vs. thrice daily (P=.004).
Quality-of-life questionnaires assessed fatigue effect and psychological
general well-being, as well as treatment preference. According to the results,
scores favored the once-daily dose for psychosocial functioning
(P=.004), cognitive functioning (P=.054) and total score
(P=.08) vs. the thrice-daily dose. At 12 weeks, 85% of patients assessed
the preference of once-daily dosing vs. thrice-daily dosing as large or very
large (P<.0001), and 59 of 64 patients chose to continue into the
extension phase of the trial, the researchers said.
“The once-daily dosing achieved a high and reliable bioavailability
and consistent exposure [serum] cortisol profile more resembling normal
physiology, avoiding the last two peaks during thrice-daily, all of which may
be of importance for improving outcome in
adrenal insufficient patients,” they wrote.