Table 4 PK and PD changes of ROF and ROF N-oxide in DDIs

KET

ROF: Repeated-doses of 0.5 mg OD from days 1 to 11; KET: A single dose of 200 mg on day 11

ROF

1.43

1.07

-

1.34

1.06

NR

ROF N-oxide

1.06

0.95

0.88

0.80

ROF: Single-dose of 0.5 mg OD on days 1 and 11, respectively; KET: Repeated-doses of 200 mg BID from days 8 to 20

ROF

2.07

1.18

1.34

2.01

1.23

1.10

ROF N-oxide

1.33

0.96

1.09

0.62

FLUV

ROF: Single-dose of 0.5 mg OD on day 15; FLU: Repeated-doses of 50 mg OD from days 8 to 21

ROF

2.29

1.16

1.62

2.56

1.12

1.59

ROF N-oxide

1.66

0.84

1.52

0.80

RIF

ROF: Single-dose of 0.5 mg OD on day 12; RIF: Repeated-doses of 600 mg OD from days 5 to 15

ROF

0.20

0.63

0.44

0.32

0.19

0.43

ROF N-oxide

0.44

1.28

0.49

1.30

ENO

ROF: Single-dose of 0.5 mg OD on days 1 and 12, respectively; ENO: Repeated-doses of 400 mg BID from days 2 to 19

ROF

1.22

1.19

1.21

1.58

1.20

1.25

ROF N-oxide

1.02

1.12

1.20

0.86

CIM

ROF: Single-dose of 0.5 mg OD on days 1 and 13, respectively; CIM: Repeated-doses of 400 mg BID from days 6 to 16

ROF

1.37

1.07

1.06

1.46

1.85

1.48

ROF N-oxide

1.04

0.94

0.96

1.27

ITR

Concomitantly used at repeated-doses of ITR 200 mg OD, FLU 150 mg OD, EFA 600 mg OD, respectively, and ROF 0.5 mg OD on day14

ROF

2.14

1.16

1.40

NR

NR

ROF N-oxide

1.22

0.70

FLU

ROF

1.89

1.18

1.16

ROF N-oxide

1.12

0.92

EFA

ROF

0.28

0.64

0.58

ROF N-oxide

0.60

1.16