. 2025 Oct 8;23:546. doi: 10.1186/s12916-025-04364-9

Table 3.

PK parameters of the parent drug bireociclib after multiple doses (geometric mean)—PK parameter set

	QD	BID
C_ss,max (ng/mL)	110.8 (21.6)	323.9 (170.7)	273.9 (58.0)	435.0 (75.1)	326.6 (58.1)	394.1 (30.4)	276.0 (46.2)	282.2 (51.5)	403.6 (59.8)
C_ss,min (ng/mL)	24.3 (115.7)	167.0 (288.1)	65.2 (98.5)	165.7 (66.4)	107.2 (58.3)	139.3 (42.5)	142.8 (71.4)	156.9 (66.3)	257.5 (79.4)
AUC_ss,0-t (h × ng/mL)	1463.6 (50.2)	5868.3 (243.3)	3758.7 (68.6)	6841.5 (70.7)	4825.9 (57.8)	6321.7 (29.5)	4228.7 (55.7)	4243.5 (59.3)	7194.3 (72.4)
AUC_ss,0–12 (h × ng/mL)	961.5 (42.1)	3137.5 (184.2)	2368.3 (59.4)	3993.5 (72.7)	2977.4 (59.7)	3704.7 (29.6)	2600.2 (51.8)	2720.2 (55.2)	4019.1 (65.7)
AUC_{ss, 0-tau} (h × ng/mL)	1466.8 (51.0)	5869.4 (237.0)	3785.8 (68.8)	6861.9 (70.9)	4818.3 (62.8)	6225.7 (32.8)	2600.2 (51.8)	2720.2 (55.2)	4019.1 (65.7)
T_{ss, max} (h)*	5.0 (4.0–6.0)	5.0 (4.1–6.0)	4.0 (4.0–6.0)	6.0 (4.0–6.1)	6.0 (4.0–7.9)	6.0 (3.9–8.1)	5.0 (3.7–8.0)	4.0 (2.0–6.0)	4.0 (0.0–8.0)
Swing	3.395 (116.2)	0.884 (78.4)	3.031 (91.6)	1.611 (24.8)	2.017 (31.9)	1.752 (54.1)	0.857 (67.7)	0.753 (51.3)	0.506 (70.9)

BID

80 mg
(N = 2)

160 mg
(N = 3)^†

240 mg
(N = 6)

320 mg
(N = 4)

420 mg
(N = 10)

560 mg
(N = 20)

240 mg
(N = 8)

360 mg
(N = 11)

480 mg
(N = 19)

C_ss,max (ng/mL)

110.8

(21.6)

323.9

(170.7)

273.9

(58.0)

435.0

(75.1)

326.6

(58.1)

394.1

(30.4)

276.0

(46.2)

282.2

(51.5)

403.6

(59.8)

C_ss,min (ng/mL)

24.3

(115.7)

167.0

(288.1)

65.2

(98.5)

165.7

(66.4)

107.2

(58.3)

139.3

(42.5)

142.8

(71.4)

156.9

(66.3)

257.5

(79.4)

AUC_ss,0-t (h × ng/mL)

1463.6

(50.2)

5868.3

(243.3)

3758.7

(68.6)

6841.5

(70.7)

4825.9

(57.8)

6321.7

(29.5)

4228.7

(55.7)

4243.5

(59.3)

7194.3

(72.4)

AUC_ss,0–12 (h × ng/mL)

961.5

(42.1)

3137.5

(184.2)

2368.3

(59.4)

3993.5

(72.7)

2977.4

(59.7)

3704.7

(29.6)

2600.2

(51.8)

2720.2

(55.2)

4019.1

(65.7)

AUC_{ss, 0-tau} (h × ng/mL)

1466.8

(51.0)

5869.4

(237.0)

3785.8

(68.8)

6861.9

(70.9)

4818.3

(62.8)

6225.7

(32.8)

2600.2

(51.8)

2720.2

(55.2)

4019.1

(65.7)

T_{ss, max} (h)*

5.0

(4.0–6.0)

5.0

(4.1–6.0)

4.0

(4.0–6.0)

6.0

(4.0–6.1)

6.0

(4.0–7.9)

6.0

(3.9–8.1)

5.0

(3.7–8.0)

4.0

(2.0–6.0)

4.0

(0.0–8.0)

Swing

3.395

(116.2)

0.884

(78.4)

3.031

(91.6)

1.611

(24.8)

2.017

(31.9)

1.752

(54.1)

0.857

(67.7)

0.753

(51.3)

0.506

(70.9)

Data are presented as the geometric mean (geometric coefficient of variation). QD group: tau = 24 h; BID: tau = 12 h.*T_{ss, max} is presented as the median (min–max).^†The PK parameter values of only one patient in the dose group are shown. AUC_ss,0-t area under the curve from zero to the final quantifiable steady state concentration; AUC_ss,0-12 area under the curve at steady state between 0 and 12 h; AUC_ss,0-tau area under the curve at steady state over a dosing interval; BID twice-daily; C_ss,max maximum steady-state plasma concentration; C_ss,min minimum steady-state plasma concentration; PK pharmacokinetic; QD once-daily; T_ss,max time to reach the maximum steady-state plasma concentration; Swing (peak-to-trough fluctuation), quantifies the fluctuations in the extent of plasma drug concentration variability following multiple doses of bireociclib, Swing = (C_ss,maxC_ss,min)/C_ss,min.