生物学的同等性とバイオアベイラビリティのジャーナル

概要

Bioequivalence Studies of Two Calcitriol Capsules Formulation in Healthy Chinese Subjects under Fasting and Fed Conditions: The Randomized, Open-Label, Single-Dose, Crossover Studies

Na Ni, Yangsheng Chen, Shengjun Qu, Junlong Wang, Lei Wang, Bin Zhou

Background: To evaluate the bioequivalence between test and reference formulations of calcitriol capsules under fasting and fed conditions and to assess their Pharmacokinetic (PK) and safety profiles.

Methods: A randomized, open-label, single-dose, crossover studies were conducted in healthy Chinese subjects. Test calcitriol capsules (T) or reference calcitriol capsules (R, 4.0 μg, 8 dosage units with the strengths of 0.5 μg per capsules) were randomly given to subjects under fasting (3-way 3-period crossover), with an administration sequence of T-R-R, R-T-R or R-R-T and fed (2-way 2-period crossover), with an administration sequence of T-R or R-T conditions, while each single administration was followed by a 14-day washout period. The plasma concentration and corresponding PK parameters of calcitriol were determined. The two formulations were considered to be bioequivalent if the 90% Confidence Intervals (CI) of the Geometric Mean (GM) ratio (T/R) for C_max, AUC_0-t and AUC_0-inf were all within the range of 80%-125%. Safety assessments including vital signs, physical examination, laboratory examination, 12-lead Electrocardiogram (ECG) and reports of Adverse Events (AE) were carefully documented.

Results: A total of 66 subjects (36 in fasting study and 30 in fed study) were randomized and all completed with the samples collected. 2 subjects (1 in fasting study and 1 in fed study) lost when follow up of AE, one month after the studies. The 90% CI of the GM ratio for C_max , AUC_0-t and AUC_0-inf , respectively, were 100.59%-112.86%, 99.79%-110.84%, and 99.30%-108.22% under the fasting condition and 99.25%-119.86%, 99.17%-111.58% and 97.83%-110.00% under the fed condition. In fasting study, 10(27.78%, n=36) experienced 15 AEs after the administration of T, and 25 (34.72%, n=72) experienced 34 AEs after the administration of R. In fed study, 14 (46.67%, n=30) experienced 24 AEs after the administration of T, and 5 (16.67%, n=30) experienced 7 AEs after the administration of R. Only one AE of no drug-related was grade 2. The incidence of AEs and drug-related AEs were similar between T and R (all P>0.05) and no serious AE occurred during the studies.

Conclusions: T and R were bioequivalent and well tolerated in healthy Chinese subjects under fasting and fed conditions.