OBJECTIVE

2

To evaluate the bioequivalence of a single oral administration of two palbociclib preparations in healthy subjects under fasting and fed conditions.

METHODS

2

Twenty-four healthy subjects （fasting test） and twenty healthy subjects （fed test） were enrolled and divided into two groups. A single-center， open-label， single-dose， two-formulation， two-period， two-sequence and crossover trial was designed. The subjects in the two groups were given the test preparation （domestic Palbociclib capsules） or the reference preparation （original Palbociclib capsules） orally under fasting or fed conditions respectively followed by a 14-day washout period. The blood samples were collected at different time points before and after treatment. After pretreatment， the mass concentration of palbociclib

in vivo

was determined by high-performance liquid chromatography-tandem mass spectrometry with palbociclib-

d

8

as the internal standard. SAS V9.4 software was used to calculate the pharmacokinetic parameters and evaluate the bioequivalence.

RESULTS

2

Under fasting condition， the

c

max

of the test preparation and the reference preparation were （71.4±18.1） and （73.8±19.0） ng/mL； AUC

0－

t

were （1 754±412） and （1 793±448） h·ng/mL； AUC

0－∞

were （1 851±456） and （1 887±478） h·ng/mL， respectively. Under fed condition， th

e

c

max

of the test preparation and the reference preparation were （78.4±18.3） and （81.9±21.7） ng/mL； AUC

0－

t

were （1 905±375） and （1 932±318） h·ng/mL； AUC

0－∞

were （2 027±411） and （2 050±342） h·ng/mL， respectively. The 90%CI of the geometric mean ratio of the above parameters was within the acceptable range （80.00%-125.00%）. Under fasting and fed conditions， there were 20 and 16 adverse events in 9 and 8 subjects， respectively， but no serious adverse event was observed.

CONCLUSIONS

2

Under the fasting and fed conditions， the test preparation and the reference preparation of Pibociclib capsules are bioequivalent and have comparable safety.