Observed mean PK parameters for FMO substrates using hepatocyte data
| Drug | Dosing Regimen | Dose | Observed AUC (S.D.) | Observed Cmax (S.D.) | Observed CL (S.D.) | Predicted AUC with Hep (S.D) | Predicted Cmaxa with Heps (S.D) | Predicted CL (S.D.) | Reference for the Observed Data |
|---|---|---|---|---|---|---|---|---|---|
| mg | ng⋅h/ml | ng/ml | l/h | ng⋅h/ml | ng/ml | l/h | |||
| Benzydamine | Intravenous | 5 | 540 (112) | 68 (19) | 9.6 | 594 (191) | 74 (18) | 8.89 (3.2) | Baldock et al. (1991) |
| Benzydamine | Oral | 50 | 4994 (1190) | 546 (177) | 9.8 | 4245 (1748) | 398 (126) | 9.4 (3.2) | Baldock et al. (1991) |
| Itopride | Oral | 50 | 750 (123) | 280 (49) | NR | 1440 (424) | 353 (61) | 37.6 (11) | http://www.meppo.com/pdf/drugs/2845-GANATON-1415104080.pdf |
| Itopride | Oral | 150 | 2170 (349) | 930 (50) | 55–88 | 1940 (442)b | 1061 (184) | 81 (18) | Katagiri et al. (2006) |
| Tozasertib | IV | 4212 | 77,673 (18,560) | 3547 (1113)a | 53.6 (17.6) | 85,135 (20,883) | 3480 (797) | 47 (11) | Traynor et al. (2011) |
| Tamoxifen | Oral (multiple doses) | 20 | 2336 (699) | 134.8 (35.5) | 7.68 (2.2) | 1938 (488) | 94 (22) | 11 (4) | AstraZeneca internal datac |
| Tamoxifen | Oral | 30 | 3370 (701) | 63.6 (11.1) | NR | 2379 (580) | 58 (15) | 14 (4) | Fuchs et al. (1996) |
| Moclobemide | Intravenous | 150 | 3807 | 2100 | 39.4 (5.9) | 4180 (738) | 3825 (376) | 36(6) | Raaflaub et al. (1984) |
| Moclobemide | Oral | 100 | 1570 | 823 | 63.7 | 1859 (459) | 531 (138) | 57 (18) | Schoerlin et al. (1987) |
| Imipramine | Intravenous | 1 | 28 (12–22) | (0.35–0.60) | 39.5 (33.6–63) | 16 (4) | 0.9 (0.3) | 65 (13) | Nguyen et al. (2016) |
| Imipramine | Oral | 100 | 985 (662) | 63.2 (40) | 126 (88) | 1663 (614) | 46 (17) | 69 (28) | Albers et al. (2000) |
| Clozapine | Oral | 100 | 3994 (2144) | 185 (132) | 31.81 (16) | 5465 (2097) | 493 (179) | 21 (9) | Tassaneeyakul et al. (2005) |
| Olanzapine | Oral | 10 | 823 (480);AUC0–120 h | 21.4 (14) | 13 (4.6) | 623 (197) | 20 (6) | 18 (7) | Chiu et al. (2004) |
| Ranitidine | Intravenous | 20 | 488 (40) | 615 | 43 (3.7) | 470 (99) | 891 (108) | 49 (14) | McNeil et al. (1981) |
| Ranitidine | Oral | 100 | 1726 (418) | 342 (122) | NR | 1551 (388) | 280 (48) | 68 (17) | McNeil et al. (1981) |
heps, hepatocytes; NR, not reported. —, data not available or not reported.
↵a Cmax = concentration at the end of infusion.
↵b AUC0–4 h to match the reported AUC.
↵c Clinical trial NCT02093351: To assess safety and effect of olaparib on the pharmacokinetics of anastrozole, letrozole, and tamoxifen, and their effect on olaparib, in patients with advanced solid cancer (2017).