evaluation of the pharmacokinetic drug interaction potential of tivantinib arq 197 using cocktail probes in patients with advanced solid tumours aims this phase 1 openlabel crossover study sought to evaluate drugdrug interactions between tivantinib and cytochrome p450 cyp substrates and tivantinib and pglycoproteinmethods the effect of tivantinib doses on the pharmacokinetics of the probe drugs for cyp1a2 caffeine cyp2c9 swarfarin cyp2c19 omeprazole and cyp3a4 midazolam and for pglycoprotein 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 dailyresults the ratios of geometric least squares mean 90 confidence interval for the area under the concentrationtime curve from time zero to the last quantifiable concentration in the presenceabsence of tivantinib were 097 089105 for caffeine 088 076102 for swarfarin 089 060131 for omeprazole 083 067102 for midazolam and 069 051094 for digoxin similar effects were observed for maximum plasma concentrations the ratio for digoxin in the presenceabsence of tivantinib was 075 060095conclusions 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 pglycoprotein substrates when administered with tivantinib