Blood sample collection and bioanalysis
Blood samples (3, 7 or 10 mL per sample) for measurement of plasma
concentration of digoxin and rosuvastatin were collected before the
administration of capmatinib (Day 1 to Day 11 of DDI phase) and after
the administration (Day 22 to Day 32 of DDI phase), at various time
points (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96,
120, 144, 168, 192, 216 and 240 hours post-dose). Blood samples for
measurement of pharmacokinetics of capmatinib were collected during the
DDI phase (pre-dose on Day 22) and post-DDI phase (pre-dose and 2 hours
post-dose on Cycle 2 Day 1).
Plasma concentrations of digoxin, rosuvastatin and capmatinib were
determined using a validated liquid chromatography-tandem mass
spectrometry assay with a lower limit of quantification of approximately
0.05, 0.05, and 1.00 ng/mL for digoxin, rosuvastatin and capmatinib,
respectively.