Table 3.

Inputs used within SIMCYP to predict the DDIs for 20 victim compounds when co-administered with the CYP3A4 inhibitor ketoconazole, under steady state conditions

		Pharmacokinetic inputs				In vitro measurements			Clinical information
Compound	MW	fuplasma	fumic	Renal clearance (l h−1)	B : P ratio*	Intrinsic clearance (μl min−1 mg−1)	fm CYP		Dose	Ketoconazole
1.eletriptan	383	0.240	0.99	–	2.42	16.0	1A2 2C9 2C19 2D6 3A4	0.00 0.00 0.89 9.17 89.94	80 mg qd	400 mg qd × 4 days
2.tolteradine	326	0.037	0.65	Low	1.61	77.5	1A2 2C9 2C19 2D6 3A4	0.00 0.00 5.13 66.71 28.15	2 mg qd	400 mg qd × 4 days
3.celecoxib	391	0.030	0.09	–	–	223.2	1A2 2C9 2C19 2D6 3A4	1.56 88.90 1.45 5.06 3.03	200 mg qd	200 mg bd × 7 days
4.alprazolam	309	0.290	0.48	–	1.06	<9	1A2 2C9 2C19 2D6 3A4	0.00 0.00 0.00 0.00 100.00	1 mg qd	200 mg bd × 7 days
5.triazolam	343	0.100	0.66	Low	0.65	37.8	1A2 2C9 2C19 2D6 3A4	0.00 0.00 0.00 0.00 100.00	0.25 mg qd	200 mg bd × 7 days
6.conivaptin	499	0.050	0.14	–	–	119.7	1A2 2C9 2C19 2D6 3A4	0.00 0.00 0.00 0.00 100.00	10 mg qd	200 mg bd × 7 days
7.eplerenone	415	0.600	0.92	Low	–	<9	1A2 2C9 2C19 2D6 3A4	0.00 0.00 0.00 0.00 100.00	100 mg qd	200 mg bd × 7 days
8.lasofoxifene	414	0.001	0.05	Low	–	77.0	1A2 2C9 2C19 2D6 3A4	0.00 0.00 0.00 8.19 91.81	0.25 mg qd	400 mg qd × 20 days
9.tirilazed	624	0.006	0.01	Low	–	1264.4	1A2 2C9 2C19 2D6 3A4	0.00 0.00 0.00 0.12 99.88	100 mg qd	200 mg bd × 7 days
10.ziprasidone	413	0.010	0.08	Low	0.74	256.7	1A2 2C9 2C19 2D6 3A4	0.00 5.87 0.21 0.25 93.68	40 mg qd	200 mg qd 1 day then 400 mg qd × 4 days
11.dofetilide	442	0.360	0.52	14.6	0.62	<9	1A2 2C9 2C19 2D6 3A4	0.00 0.00 0.00 0.00 100.00	0.5 mg qd	400 mg qd × 7 days
12.PF-A	408	0.002	0.06	–	–	733.3	1A2 2C9 2C19 2D6 3A4	5.96 28.52 14.78 0.00 50.74	0.6 mg qd	200 mg bd × 7 days
13.PF-B	506	0.420	0.62	–	–	39.6	1A2 2C9 2C19 2D6 3A4	0.000 0.000 0.000 0.000 100.00	3 mg bid	200 mg bid × 8 days
14.PF-C	507	0.070	0.42	–	–	27.3	1A2 2C9 2C19 2D6 3A4	0.00 0.00 0.00 0.00 100.00	3 mg qd	400 mg qd × 9 days
15.PF-D	583	0.380	0.64	–	–	38.0	1A2 2C9 2C19 2D6 3A4	0.00 0.00 1.33 0.00 98.67	200 mg qd	400 mg qd × 6 days
16.PF-E	520	0.330	1.00	LOW	2.42	21.4	1A2 2C9 2C19 2D6 3A4	0.00 0.00 0.00 0.00 100.00	100 mg qd	400 mg qd × 7 days
17.PF-F	274	0.060	0.30	LOW	2.1	91.7	1A2 2C9 2C19 2D6 3A4	19.03 18.35 42.99 2.08 17.54	30 mg qd	400 mg qd × 4 days
18.PF-G	448	0.004	0.04	–	–	1343.0	1A2 2C9 2C19 2D6 3A4	0.00 1.96 1.50 3.12 93.43	10 mg qd	200 mg bd × 16 days
19.PF-H	427	0.033	0.38	LOW	–	19.0	1A2 2C9 2C19 2D6 3A4	0.00 0.00 0.00 7.20 92.80	10 mg qd	400 mg qd × 13 days
20.PF-I	396	0.012	1.00	0.24	–	<9	1A2 2C9 2C19 2D6 3A4	0.00 0.00 0.00 0.00 100.00	100 mg qd	400 mg qd × 5 days

^*B:P values depicted by (−) indicate no in house measure was available, consequently a default value of 0.55 was used.