Table 3.
Efavirenz, atazanavir and ritonavir plasma pharmacokinetic parameters on study Day 0, before vaginal ring contraceptive insertion, and Day 21, in combination with the vaginal ring contraceptive
| Pharmacokinetic parameter | Study day | N |
Median (IQR) |
Geometric Mean (95% CI) |
Geometric Mean Ratio (90% CI) |
Wilcoxon signed rank p–value |
| Cmax (ng/mL) | 0 | 24 | 4,541 (3,321 – 6,720) | 4,868 (3,778 – 6,273) | ||
| 21 | 24 | 3,786 (3,289 – 6,724) | 4,717 (3,699 – 6,014) | 0·97 (0·85 – 1·11) | 0·72 | |
| Cmin (ng/mL) | 0 | 24 | 2,122 (1,435 – 2,703) | 2,353 (1,714 – 3,231) | ||
| 21 | 24 | 1,766 (1,174 – 2,351) | 1,504 (854 – 2,646) | 0·64 (0·42 – 0·97) | 0·020 | |
| AUC0–8h (ng*h/mL)a | 0 | 24 | 26,974 (21,035 – 42,834) | 30,768 (23,419 – 40,422) | ||
| 21 | 24 | 24,937 (17,731 – 41,999) | 27,551 (20,782 – 36,525) | 0·90 (0·79 – 1·01) | 0·14 | |
| AUC0–24h, (ng*h/mL)a | 0 | 24 | 68,949 (51,162 – 108,194) | 79,049 (59,545 – 104,941) | ||
| 21 | 24 | 57,796 (42,701 – 113,611) | 69,129 (51,318 – 93,120) | 0·87 (0·77 – 0·99) | 0·031 | |
| Pharmacokinetic parameter | Study day | N |
Median (IQR) |
Geometric Mean (95% CI) |
Geometric Mean Ratio (90% CI) |
Wilcoxon signed rank p–value |
| Cmax (ng/mL) | 0 | 23 | 4,291 (3,112 – 5,496) | 3,717 (2,891 – 4,780) | ||
| 21 | 23 | 3,583 (2,726 – 4,124) | 2,828 (1,932 – 4,139) | 0·76 (0·55 – 1·05) | 0·049 | |
| Cmin (ng/mL) | 0 | 23 | 797 (489 – 1,417) | 641 (379 – 1,084) | ||
| 21 | 23 | 599 (226 – 1,096) | 451 (256 – 794) | 0·70 (0·41 – 1·21) | 0·17 | |
| AUC0–8h (ng*h/mL)a | 0 | 22 | 20,560 (16,651 – 28,438) | 19,726 (15,367 – 25,320) | ||
| 21 | 22 | 18,324 (13,160 – 21,654) | 14,678 (9,805 – 21,973) | 0·75 (0·52 – 1·08) | 0·10 | |
| AUC0–24h, (ng*h/mL)a | 0 | 23 | 44,314 (31,525 – 51,744) | 38,992 (30,558 – 49,754) | ||
| 21 | 23 | 36,765 (22,246 – 49,836) | 29,882 (20,725 – 43,086) | 0·77 (0·57 – 1·03) | 0·077 | |
| Pharmacokinetic parameter | Study day | N |
Median (IQR) |
Geometric Mean (95% CI) |
Geometric Mean Ratio (90% CI) |
Wilcoxon signed rank p–value |
| Cmax (ng/mL) | 0 | 23 | 1,437 (982 – 2,274) | 1,351 (1,062 – 1,719) | ||
| 21 | 23 | 1,063 (742 – 1,472) | 790 (473 – 1,321) | 0·59 (0·38 – 0·91) | 0·0046 | |
| Cmin (ng/mL) | 0 | 23 | 70 (41 – 124) | 73 (42 – 126) | ||
| 21 | 23 | 52 (25 – 95) | 49 (29 – 81) | 0·67 (0·38 – 1·19) | 0·30 | |
| AUC0–8h (ng*h/mL)a | 0 | 22 | 6,746 (5,340 – 11,026) | 6,921 (5,466 – 8,764) | ||
| 21 | 22 | 5,352 (3,900 – 7,615) | 4,634 (2,997 – 7,165) | 0·66 (0·46 – 0·96) | 0·0018 | |
| AUC0–24h, (ng*h/mL)a | 0 | 23 | 10,740 (7,778 – 15,538) | 10,875 (8,534 – 13,856) | ||
| 21 | 23 | 7,211 (5,855 – 11,874) | 6,865 (4,524 – 10,419) | 0·63 (0·45 – 0·89) | 0·0082 |
Abbreviations: AUC, area under the concentration time curve; Cmax, maximum concentration; Cmin, minimum concentration.
a
Estimated value based on linear up, log down trapezoidal rule (Phoenix® WinNonLin® version 7.0; Certara USA, Inc., Princeton, NJ)