Results of transport studies for 3 μM [14C]lapatinib in MDCKII-MDR1 or MDCKII-BCRP cell monolayers
Data are the means ± S.D. from three monolayers over 90 min for MDR1- and 180 min for BCRP-expressing MDCKII monolayers. All donor compartments contained Lucifer yellow (100 μM) to determine monolayer integrity. Amprenavir served as a positive control for Pgp efflux and cimetidine for BCRP efflux. The measured radiochemical purity of [14C]lapatinib was >97%, and no metabolic or chemical degradation was detected during the studies.
| MDCKII Cell Line | GF120918a | Rate A→B | Rate B→A | Apical Efflux Ratio | A→B Mass Balance | B→A Mass Balance | P7.4 |
|---|---|---|---|---|---|---|---|
| pmoles/min/cm2 | % | nm/s | |||||
| MDR1 | - | 0.06 ± 0.01 | 0.98 ± 0.06 | 15 | 85 ± 5.9 | 88 ± 0.2 | |
| MDR1 | + | 0.61 ± 0.03 | 0.20 ± 0.01 | 0.33 | 82 ± 5.3 | 100 ± 1.0 | 11 ± 0.2 |
| BCRP | - | 0.027 ± 0.004 | 0.071 ± 0.002 | 2.6 | 92 ± 4.7 | 95 ± 2.7 | |
| BCRP | + | 0.046 ± 0.008 | 0.047 ± 0.001 | 1.0 | 90 ± 5.4 | 97 ± 3.8 | 2.7 ± 0.2 |
↵ a GF120918 was used in both donor and receiver compartments at 2 μM for Pgp and 5 μM for BCRP.