Summary
Aim
This phase 1, open-label, crossover study sought to evaluate drug–drug interactions between tivantinib and cytochrome P450 (CYP) substrates and tivantinib and P-glycoprotein.
Methods
The effect of tivantinib doses on the pharmacokinetics of the probe drugs for CYP1A2 (caffeine), CYP2C9 (warfarin), CYP2C19 (omeprazole), and CYP3A4 (midazolam), and for P-glycoprotein (digoxin) was investigated in 28 patients with advanced cancer using a cocktail probe approach. Patients received single doses of probe drugs alone and after 5 days of treatment with tivantinib 360 mg twice daily.
Results
The ratios of geometric least squares mean (90% confidence interval) for the area under the concentration–time curve from time zero to the last quantifiable concentration in the presence/absence of tivantinib were 0.97 (0.89–1.05) for caffeine; 0.88 (0.76–1.02) for S-warfarin; 0.89 (0.60–1.31) for omeprazole; 0.83 (0.67–1.02) for midazolam; and 0.69 (0.51–0.94) for digoxin. Similar effects were observed for maximum plasma concentrations; the ratio for digoxin in the presence/absence of tivantinib was 0.75 (0.60–0.95).
Conclusions
The data suggest that tivantinib 360 mg twice daily has either a minimal or no effect on the pharmacokinetics of probe drugs for CYP1A2, CYP2C9, CYP2C19, and CYP3A4 substrates, and decreases the systemic exposure of P-glycoprotein substrates when administered with tivantinib.
http://ift.tt/2iQIIbu
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου
Σημείωση: Μόνο ένα μέλος αυτού του ιστολογίου μπορεί να αναρτήσει σχόλιο.