3.3 PK analyses
The plasma concentrations of SHR2554 were significantly decreased and
its elimination rate remarkably increased when coadministration with
rifampin compared to SHR2554 administration alone (Figure 2 A,
B) . The PK parameters of SHR2554 for SHR2554 administration alone and
coadministration with rifampin were summarized inTable 2 .
Compared to administration of SHR2554 as monotherapy and
coadministration with rifampin, the geometric mean
AUC0-t of SHR2554 in plasma was 528.0 and 35.5 h*ng/mL,
the geometric mean AUC0-∞ was 581.7 and 42.4 h*ng/mL,
the geometric mean Cmax was 136.7 and 42.4 ng/mL, the
median Tmax was 1.8 hours and 1.6 hours, the mean
t1/2 was 6.5 and 2.6 hours, the geometric mean of Cl/F
was 540.3 and 7468.3 L/h, and the geometric mean of VZ/F was 4829.1 L
and 27346.1 L, respectively. According to these results, we could found
that concomitant use of rifampin significantly alters the exposure,
elimination half-life, and apparent clearance of SHR2554, in addition,
combination with rifampin affected the intra-subject variability to
varying extents.
The results in the mixed-effect model analysis showed that the
least-squares geometric mean ratio (rifampin coadministration/SHR2554
administration) and 90% CI of AUC0-t,
AUC0-∞ and Cmax of SHR2554 were 0.11
(0.08, 0.15), 0.07 (0.05, 0.09), and 0.07 (0.05, 0.10), respectively,
which indicated SHR2554 coadministration with rifampin significantly
reducing AUC0-t, AUC0-∞ and
Cmax of SHR2554 of 89%, 93%, and 93%, respectively
(Table 3) .