TABLE 2.
Comparison of raltegravir plasma PK for HIV-1-infected patients administered multiple doses of raltegravir with and without coadministration of multiple doses of TDF and lamivudinea
| Parameter and raltegravir treatment | nb | GM (90% CI)
|
||
|---|---|---|---|---|
| Wk 2 of part II | Day 10 of part I | GMR of wk 2 of part II to day 10 of part Ic | ||
| AUC0-12 (μM h−1) | ||||
| All doses | 25 | 13.9 (10.8-18.0) | 9.9 (7.7-12.6) | 1.41 (1.11-1.79) |
| 100 mg b.i.d. | 6 | 5.4 (2.9-9.9) | 5.5 (4.2-7.2) | 0.98 (0.57-1.67) |
| 200 mg b.i.d. | 7 | 14.9 (12.2-18.2) | 9.4 (6.8-13.1) | 1.58 (1.16-2.15) |
| 400 mg b.i.d. | 6 | 25.3 (20.9-30.8) | 14.3 (7.6-26.7) | 1.78 (0.86-3.66) |
| 600 mg b.i.d. | 6 | 18.3 (10.6-31.6) | 12.9 (5.8-28.4) | 1.42 (0.73-2.78) |
| Cmax (μM) | ||||
| All doses | 25 | 4.2 (3.0-5.9) | 3.2 (2.4-4.3) | 1.33 (0.96-1.85) |
| 100 mg b.i.d. | 6 | 1.2 (0.5-3.0) | 2.0 (1.3-3.1) | 0.63 (0.28-1.40) |
| 200 mg b.i.d. | 7 | 4.6 (3.6-6.0) | 3.3 (1.9-5.9) | 1.39 (0.89-2.17) |
| 400 mg b.i.d. | 6 | 8.6 (6.5-11.3) | 4.5 (2.0-10.2) | 1.90 (0.76-4.77) |
| 600 mg b.i.d. | 6 | 6.3 (3.2-12.4) | 3.3 (1.4-8.1) | 1.89 (0.94-3.80) |
| C12 (nM) | ||||
| All doses | 25 | 147.7 (100.5-217.0) | 103.7 (77.6-138.6) | 1.42 (0.89-2.28) |
| 100 mg b.i.d. | 6 | 155.1 (72.5-331.5) | 45.0 (22.8-89.1) | 3.44 (1.40-8.46) |
| 200 mg b.i.d. | 7 | 182.6 (98.5-338.6) | 112.4 (78.4-161.1) | 1.62 (1.01-2.61) |
| 400 mg b.i.d. | 6 | 239.2 (150.2-381.0) | 141.7 (87.6-229.1) | 1.69 (1.12-2.54) |
| 600 mg b.i.d. | 6 | 67.7 (16.3-280.6) | 159.3 (71.8-353.4) | 0.43 (0.07-2.41) |
Subjects were administered multiple doses of raltegravir twice daily (b.i.d.) with and without coadministration of multiple doses of TDF (300 mg once daily) and lamivudine (300 mg once daily).
n represents the number of patients who had intensive PK data at both week 2 of part II and day 10 of part I in the treatment group.
The GMR is the ratio of the GM of PK parameters from cohort I subjects at week 2 of the combination therapy phase (part II) to those on day 10 of the monotherapy phase (part I). The CI was calculated based on the paired t distribution. (Note that raltegravir was administered with tenofovir and lamivudine in part II; raltegravir was administered alone in part I.)