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

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, AUC and AUC. Monitoring of adverse events throughout the study. Results： The 90% confidence intervals of the test/reference AUC ratio and C ratio were within the acceptance criteria. Under the fasting condition, T 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.