15 days; Day 14 doses were administered after a 15%-fat breakfast (757 Kcal) and 9%-fat evening snack (236 Kcal), and Day 15 doses were administered after a 15%-fat breakfast (757 Kcal) and 32%-fat dinner (815 Kcal). Indinavir Cmin was also increased 4-fold. Effects were assessed relative to an indinavir 800 mg q8h regimen under fasting conditions.
2 Effects were assessed on a dose-normalized comparison to a methadone 20 mg single dose.
3 Sulfamethoxazole and trimethoprim taken as single combination tablet.
4 90% CI presented for R- and S-warfarin AUC and Cmax ratios.
5 This significant increase in plasma fluticasone propionate exposure resulted in a significant decrease (86%) in plasma cortisol AUC.
↑ Indicates increase.
↓ Indicates decrease.
↔ Indicates no change.
* Parallel group design; entries are subjects receiving combination and control regimens, respectively.
Alprazolam 1, single dose 500 q12h, 10 d 12 ↓ 12% (-5,30%) ↓ 16% (5, 27%) ND
Clarithromycin
14-OH clarithromycin metabolite 500 q12h, 4 d 200 q8h, 4 d 22 ↑ 77% (56, 103%)
↓ 100% ↑ 31% (15, 51%)
↓ 99% ↑ 2.8-fold (2.4, 3.3X)
↓ 100%
Desipramine
2-OH desipramine metabolite 100, single dose 500 q12h, 12 d 14 ↑ 145% (103, 211%)
↓ 15% (3, 26%) ↑ 22% (12, 35%)
↓ 67% (62, 72%) ND
ND
Didanosine 200 q12h, 4 d 600 q12h, 4 d 12 ↓ 13% (0, 23%) ↓ 16% (5, 26%) ↔
Ethinyl estradiol 50 µg single dose 500 q12h, 16 d 23 ↓ 40% (31, 49%) ↓ 32% (24, 39%) ND
Fluticasone propionate aqueous nasal spray 200 mcg qd, 7 d 100 mg q12h, 7d 18 ↑ approximately 350-fold5 ↑ approximately 25-fold5
Indinavir1
Day14
Day 15 400 q12h, 15 d 400 q12h, 15 d 10
↑ 6% (-14, 29%)
↓ 7% (-22, 28%)
↓ 51% (40, 61%)
↓ 62% (52, 70%) ↑ 4-fold (2.8,6.8X)
↑ 4-fold (2.5,6.5X)
Ketoconazole 200 daily, 7 d 500 q12h, 10 d 12 ↑ 3.4-fold (2.8, 4.3X) ↑ 55% (40, 72%) ND
Meperidine
Normeperidine metabolite 50 oral single dose 500 q12h, 10 d 8
6 ↓ 62% (59, 65%)
↑ 47% (-24, 345%) ↓ 59% (42, 72%)
↑ 87% (42, 147%) ND
ND
Methadone2 5, single dose 500 q12h, 15 d 11 ↓ 36% (16, 52%) ↓ 38% (28, 46%) ND
Rifabutin
25-O-desacetyl rifabutin metabolite 150 daily, 16 d 500 q12h, 10 d 5,
11* ↑ 4-fold (2.8, 6.1X)
↑ 38-fold (28, 56X) ↑ 2.5-fold (1.9, 3.4X)
↑ 16-fold (13, 20X) ↑ 6-fold (3.5, 18.3X)
↑ 181-fold (ND)
Sildenafil 100, single dose 500 BID, 8 d 28 ↑ 11-fold ↑ 4-fold ND
Sulfamethoxazole3 800, single dose 500 q12h, 12 d 15 ↓ 20% (16, 23%) ↔ ND
Tadalafil 20 mg, single dose 200 mg q12h ↑ 124% ↔ ND
Theophylline 3 mg/kg q8h, 15 d 500 q12h, 10 d 13, 11* ↓ 43% (42, 45%) ↓ 32% (29, 34%) ↓ 57% (55, 59%)
Trazodone 50 mg, single dose 200 mg q12h, 4doses 10 ↑ 2.4-fold ↑ 34%
Trimethoprim3 160, single dose 500 q12h, 12 d 15 ↑ 20% (3, 43%) ↔ ND
Vardenafil 5 mg 600 q12h ↑ 49-fold ↑ 13-fold ND
Voriconazole 400 q12h, 1 d; then 200 q12h, 8 d 400 q12h, 9 d ↓ 82% ↓ 66%
Warfarin
S-Warfarin
R-Warfarin 5, single dose 400 q12h, 12d 12
↑ 9% (-17, 44%)4
↓ 33% (-38, -27%)4
↓ 9% (-16, -2%)4
↔
ND
ND
Zidovudine 200 q8h, 4 d 300 q6h, 4 d 9 ↓ 25% (15, 34%) ↓ 27
