. 2020 Sep 14;109(2):494–506. doi: 10.1002/cpt.2021

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

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

^{^a}

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

^{^b}

Net 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.

^{^c}

Unionization 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: ${Log}_{10} \frac{base (or unionized)}{acid (ionized)} = pH ‐ PKa$ .

^{^d}

Intrinsic permeability is the transcellular permeability of the unbound and unionized drug, estimated as the mean P _app,A‐B normalized by λ.