Table 1.
Effect of residual induction on dolutegravir pharmacokinetics at days 1, 7, 14, and 28 post-rifampicin, efavirenz, and rifabutin dosing
| Absence inducer | After stopping inducer | DDI ratio (residual induction) | Reference | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Observed | Predicted | Ratio P/O | Observed | Predicted | Ratio P/O | Observed | Predicted | Ratio P/O | ||
| Dolutegravir—day 1 after stopping rifampicin | ||||||||||
| Ctrough [ng/mL] | – | 749 (50) | – | – | 62 (109) | – | – | 0.08 | – | – |
| AUC0-τ [ng×h/mL] | – | 35,677 (26) | – | – | 15,549 (38) | – | – | 0.44 | – | |
| Dolutegravir—day 7 after stopping rifampicin | ||||||||||
| Ctrough [ng/mL] | – | 1068 (69) | – | – | 431 (79) | – | – | 0.40 | – | – |
| AUC0-τ [ng×h/mL] | – | 52,295 (45) | – | – | 32,154 (42) | – | – | 0.61 | – | |
| Dolutegravir—day 14 after stopping rifampicin | ||||||||||
| Ctrough [ng/mL] | – | 1070 (70) | – | – | 806 (70) | – | – | 0.75 | – | – |
| AUC0-τ [ng×h/mL] | – | 52,391 (46) | – | – | 44,172 (43) | – | – | 0.84 | – | |
| Dolutegravir—day 28 after stopping rifampicin | ||||||||||
| Ctrough [ng/mL] | – | 1070 (70) | – | – | 1046 (69) | – | – | 0.98 | – | – |
| AUC0-τ [ng×h/mL] | – | 52,391 (46) | – | – | 51,624 (46) | – | – | 0.99 | – | |
| Dolutegravir—day 1 after stopping efavirenz | ||||||||||
| Ctrough [ng/mL] | – | 910 ± 456 | – | – | 435 ± 332 | – | – | 0.48 | – | – |
| AUC0-τ [ng×h/mL] | – | 37,681 ± 9941 | – | – | 27,141 ± 8807 | – | – | 0.72 | – | |
| Dolutegravir—day 7 after stopping efavirenz | ||||||||||
| Ctrough [ng/mL] | – | 1497 ± 1050 | – | 938 ± 955 | 948 ± 698 | 1.01 | – | 0.63 | [27] | |
| AUC0-τ [ng×h/mL] | – | 60,683 ± 28,494 | – | – | 45,429 ± 19,778 | – | – | 0.75 | – | |
| Dolutegravir—day 14 after stopping efavirenz | ||||||||||
| Ctrough [ng/mL] | – | 1505 ± 1070 | – | 861 ± 627 | 1217 ± 833 | 1.41 | – | 0.81 | – | [27] |
| AUC0-τ [ng×h/mL] | – | 60,961 ± 29,091 | – | – | 53,111 ± 23,105 | – | – | 0.87 | – | |
| Dolutegravir—day 28 after stopping efavirenz | ||||||||||
| Ctrough [ng/mL] | – | 1505 ± 1071 | – | 1219 ± 710 | 1428 ± 977 | 1.17 | – | 0.95 | – | [27] |
| AUC0-τ [ng×h/mL] | – | 60,966 ± 29,113 | – | - | 58,909 ± 26,763 | - | – | 0.97 | – | |
| Dolutegravir—day 1 after stopping rifabutin | ||||||||||
| Ctrough [ng/mL] | – | 749 (50) | – | – | 554 (54) | – | – | 0.74 | – | – |
| AUC0-τ [ng×h/mL] | – | 35,677 (26) | – | – | 31,539 (27) | – | – | 0.88 | – | |
| Dolutegravir—day 7 after stopping rifabutin | ||||||||||
| Ctrough [ng/mL] | – | 1068 (69) | – | – | 934 (67) | – | – | 0.87 | – | – |
| AUC0-τ [ng×h/mL] | – | 52,294 (45) | – | – | 48,073 (43) | – | – | 0.92 | – | |
| Dolutegravir—day 14 after stopping rifabutin | ||||||||||
| Ctrough [ng/mL] | – | 1070 (70) | – | – | 1029 (69) | – | – | 0.96 | – | – |
| AUC0-τ [ng×h/mL] | – | 52,390 (46) | – | – | 51,090 (45) | – | – | 0.98 | – | |
| Dolutegravir—day 28 after stopping rifabutin | ||||||||||
| Ctrough [ng/mL] | – | 1070 (70) | – | – | 1067 (70) | – | – | 1.00 | – | – |
| AUC0-τ [ng×h/mL] | – | 52,391 (46) | – | – | 52,288 (46) | – | – | 1.00 | – | |
The results are represented as geometric mean (CV), unless otherwise specified as mean ± SD
AUC0-τ area under the concentration-time curve to tau; Ctrough trough concentration; DDI drug–drug interaction; O observed; P predicted