Pharmacokinetics and Bioequivalence of Two Formulations of Eldecalcitol
Capsules in healthy Chinese volunteers under fasting and fed conditions
and effects of food on pharmacokinetic profiles
Abstract
Aims: The objective of this study was to evaluate the
bioequivalence of two formulations of eldecalcitol (0.75 μg ) under
fasting and fed conditions, and to explore the effect of food on the
pharmacokinetic (PK) properties of eldecalcitol in healthy Chinese
volunteers. Methods: A single-center, open-label, randomized,
three-period, three-sequence, crossover study was performed in 27
healthy Chinese volunteers under fasting conditions. Meanwhile, a
two-way crossover study was performed in 28 healthy volunteers under fed
conditions. Blood samples were collected at scheduled time spots from 0
hour pre dose to 168 hours post dose following administration of 0.75 μg
eldecalcitol. The PK parameters for bioequivalence evaluation calculated
by non-compartment analysis include Cmax, AUC0-t and
AUC0-∞. Monitoring of adverse events throughout the
study. Results: The 90% confidence intervals of the
test/reference AUC ratio and Cmax ratio were within the
acceptance criteria. Under the fasting condition, Tmax
values were 3.987 h and 3.489 h in subjects after given the test and
reference formulation respectively. While in the fed study, the Tmax
were 9.006 h and 6.007 h respectively. Therefore, the Tmax was
significantly increased (P < 0.05) under fed conditions. No
severe adverse events occurred during the study and all adverse events
were mild and transient. Conclusion: The generic product of
eldecalcitol was bioequivalent to the reference product in terms of the
rate and extent of absorption under both fasting and fed conditions.
Food intake prolongs the oral absorption of eldecalcitol but does not
significantly influence the system exposure.