Rifampicin-mediated drug-drug interaction studies reported in the literature
Details of the exposure of CYP3A4 probe substrate in the before and after multiple dosing of rifampicin are shown. A negative dose stagger indicates that the victim was dosed before the perpetrator. Data are expressed as mean (coefficient of variation) with the exception of those given.
| Study | Rifampicin | Victim (Dose) | Dose Stagger | n | AUC | AUCi | 1/AUC Ratio |
|---|---|---|---|---|---|---|---|
| i.v. administration of victim drugs | ng/mL.h | ng/mL.h | |||||
| Link et al., 2008 | 600 mg daily for 6 days | MDZ (2 mg) | 24 | 8 | 126 (84–269)a | 82.4 (58.8–102)a | 1.53 |
| Kharasch et al., 2004 | 600 mg daily for 5 days | MDZ (1 mg) | 12c | 10 | 28.4 (14.1) | 14.8 (18.2) | 1.92 |
| Gorski et al., 2003 | 600 mg daily for 7 days | MDZ (0.05 mg/kg) | 12 | 52 | 118 (35.4) | 52.8 (29.7) | 2.23 |
| Phimmasone and Kharasch, 2001 | 600 mg daily for 5 days | MDZ (1 mg) | 12 | 6 | 53.0 (26.4) | 25.5 (19.0) | 2.08 |
| Szalat et al., 2007h | 600 mg daily for 7 days | MDZ (0.05 mg/kg) | 12c | 3 | 89.5 (18.3) | 51.8 (13.5) | 1.73 |
| Kharasch et al., 1997 | 600 mg daily for 5 days | MDZ (1 mg) | 24 | 9 | 72.2d (n/a) | 27.4d (n/a) | 2.64 |
| Holtbecker et al., 1996 | 600 mg daily for 7 days | NIF (0.02 mg/kg) | 0 | 6 | 38.1 (12.6) | 26.7 (44.9) | 1.43 |
| Phimmasone and Kharasch, 2001 | 600 mg daily for 5 days | ALF (0.015 mg/kg)) | 13c | 6 | 111 (52.1) | 48.2 (19.7) | 2.31 |
| Kharasch et al., 2004 | 600 mg daily for 5 days | ALF (0.015 mg/kg) | 13c | 10 | 64.8 (41.0) | 24.3 (26.7) | 2.67 |
| Kharasch et al., 2011 | 600 mg daily for 6 days | ALF (1 mg) | 9c | 6 | 59.0 (45.8) | 21.0 (38.1) | 2.81 |
| Oral administration of victim drugs | |||||||
| Backman et al., 1996 | 600 mg daily for 5 days | MDZ (15 mg) | 17 | 10 | 170 (23.4) | 7.00 (40.6) | 24.3 |
| Backman et al., 1998 | 600 mg daily for 5 days | MDZ (15 mg) | 17 | 9 | 277 (78.0) | 4.40 (68.2) | 63.0 |
| Chung et al., 2006 | 600 mg daily for 9 days | MDZ (0.075 mg/kg) | −2 | 18 | 49.0 (22–103)b | 6.10 (125–371)b | 8.03 |
| Eap et al., 2004 | 450 mg daily for 5 days | MDZ (7.5 mg) | 12c | 4 | 67.0 (44.8) | 3.50 (5.70) | 19.1 |
| Gurley et al., 2006 | 300 mg twice a day for 7 days | MDZ (8 mg) | 0c | 19 | 79.6 (29.1) | 4.55 (49.2) | 17.5 |
| Gurley et al., 2008 | 300 mg twice a day for 7 days | MDZ (8 mg) | 2 | 16 | 107 (38.0) | 6.46 (54.3) | 16.6 |
| Link et al., 2008 | 600 mg daily for 6 days | MDZ (7.5mg) | 24 | 8 | 103 (64–164)a | 1.60 (1–7.2)a | 64.3 |
| Reitman et al., 2011 | 600 mg daily for 28 days | MDZ (2 mg) | 0 | 11 | 21.4 (33.6) | 2.64 (45.3) | 8.11 |
| Kharasch et al., 2004 | 600 mg daily for 6 days | MDZ (3 mg) | 12c | 10 | 20.9 (20.1) | 1.10 (45.5) | 19.0 |
| Floyd et al., 2003 | 600 mg daily for 16 days | MDZ (2 mg; 25 mg)e | 0 | 12g | 27.1 (n/a) | 19.9 (n/a) | 17.0f |
| Gorski et al., 2003 | 600 mg daily for 7 days | MDZ (4 mg; 6 mg)e | 12 | 52 | 35.8 (58.1) | 3.70 (75.7) | 25.6f |
| Schmider et al., 1999 | 450 mg daily for 4 days | APZ (1 mg) | 0c | 4 | 242 (31.3) | 28.4 (23.9) | 8.53 |
| Chung et al., 2006 | 600 mg daily for 9 days | SMV (40 mg) | −2 | 18 | 29.0 (8–56)b | 2.60 (0.8–26)b | 11.2 |
| Kyrklund et al., 2000 | 600 mg daily for 28 days | SMV (40 mg) | 0 | 10 | 17.3 (57.2) | 2.40 (75.4) | 7.21 |
| Holtbecker et al., 1996 | 600 mg daily for 7 days | NIF (20 mg) | 0 | 6 | 230 (14.7) | 18.8 (45.7) | 12.2 |
| Villikka et al., 1997b | 600 mg daily for 5 days | ZOL (20 mg) | 17 | 8 | 1110 (36.9) | 332 (56.4) | 3.34 |
| Kharasch et al., 2004 | 600 mg daily for 6 days | ALF (0.06 mg/kg) | 13c | 10 | 103 (29.1) | 4.70 (97.9) | 21.9 |
| Kharasch et al., 2011 | 600 mg daily for 5 days | ALF (4 mg) | 12c | 6 | 108 (63.0) | 6.40 (50.0) | 16.9 |
| Villikka et al., 1997a | 600 mg daily for 5 days | TZM (0.5 mg) | 17 | 10 | 14.8 (21.4) | 0.74 (59.8) | 20.0 |
ALF, alfentanil; APZ, alprazolam; AUC, area under the curve; MDZ, midazolam; n/a, not available; NIF, nifedipine; ROA, root of administration; SMV, simvastatin; TZM, triazolam; ZOL, zolpidem.
↵a Median and range.
↵b Geometric mean and range.
↵c Ambiguous.
↵d Calculated assuming a body weight of 70 kg in both control and rifampicin arms of the study.
↵e Dose escalated for the RIF arm of the study to give equivalent MDZ concentrations as at baseline;
↵f The ratio of clearance due to dose escalation.
↵g Midazolam AUC in the absence and presence of rifampicin were calculated from oral clearances provided for 12 white subjects (all women) of the 57 subjects studied in total. Data for white men were not provided.
↵h Cerebrotendinous xanthomatosis (CTX) patients.