Table 2.

Transcellular permeability and efflux ratios of the three CDK4/6 inhibitors, determined from the parental MDCKII, MDCKII-ABCB1, and MDCKII-ABCG2 cell monolayers

	Ribociclib	Palbociclib	Abemaciclib
Parental MDCKII
Apparent permeability (Papp,A-B) (×10−6 cm/s)a	7.17 ± 1.85	9.38 ± 1.16	9.09 ± 2.21
Net efflux ratiob	1.02 ± 0.21	1.55 ± 0.17	1.03 ± 0.30
Unionization efficiency (λ)c	0.033	0.034	0.224
Intrinsic permeability (Papp,A-B/ λ)d	218.6	280.0	40.6
MDCKII-ABCB1
Apparent permeability (Papp,A-B) (×10−6 cm/s)a	1.77 ± 0.82	5.56 ± 1.10	5.65 ± 0.86
Net efflux ratiob	10.5 ± 3.30	5.92 ± 1.04	2.84 ± 0.49
MDCKII-ABCG2
Apparent permeability Papp,A-B (×10−6 cm/s)a	5.90 ± 0.91	7.73 ± 0.25	7.98 ± 0.42
Net efflux ratiob	1.02 ± 0.20	2.64 ± 1.05	1.21 ± 0.11

^aBidirectional permeability experiments were performed at pH 7.4 in both apical and basolateral chambers.

^bNet efflux ratio was the efflux ratio in the absence of an ABCB1 inhibitor (elacridar) or ABCG2 inhibitor (Ko145) divided by the efflux ratio in the presence of the inhibitor.

^cUnionization efficiency (λ) is the ratio of unionized form to total drug (the sum of unionized and ionized forms), where the unionized-to-ionized ratio is calculated based on Henderson-Hasselbalch equation: ${Log}_{10}\frac{base\left(orunionized\right)}{acid\left(ionized\right)}=pH-PKa$

^dIntrinsic permeability is the transcellular permeability of the unbound and unionized drug, estimated as the mean P_app,A-B normalized by λ.

Data are expressed as the mean ± standard deviation from at least 3 independent experiments (with duplicates in each experiment).