TABLE 2.
Median tenofovir pharmacokinetic parameters on study days 1, 8, 15, and 35
| Parametera and day | Value achieved with tenofovir DF dose of:
|
|||
|---|---|---|---|---|
| 75 mg | 150 mg | 300 mg | 600 mg | |
| AUC (ng · h/ml) | ||||
| 1 | —b | — | 2,093 | 3,372 |
| 8 | — | — | 3,179 | 4,389c |
| 15 | 717 | 1,613 | 2,937 | 6,073d |
| 35 | NDe | ND | 3,020 | 5,131 |
| Cmax (ng/ml) | ||||
| 1 | 68.6 | 111 | 240 | 618 |
| 8 | 62.9 | 130 | 375 | 573 |
| 15 | 80.8 | 163c | 303 | 633 |
| 35 | ND | ND | 326 | 498 |
| Tmax (h) | ||||
| 1 | 0.80 | 1.00 | 0.80 | 1.00 |
| 8 | 2.00c | 2.00 | 2.00 | 1.50c |
| 15 | 2.00 | 2.50 | 3.00 | 2.50d |
| 35 | ND | ND | 2.30 | 2.00 |
| t1/2 (h) | ||||
| 1 | — | — | 11.9 | 13.0 |
| 8 | — | — | 11.7 | 11.9 |
| 15 | — | 12.0 | 13.7 | 12.1 |
| 35 | ND | ND | 14.4 | 15.4 |
| CL/F (ml/h/kg) | ||||
| 1 | — | — | 910 | 1,083 |
| 8 | — | — | 584 | 671c |
| 15 | 354 | 555 | 521 | 683d |
| 35 | ND | ND | 510 | 641 |
| CLrenal/F (ml/h/kg) | ||||
| 1 | — | — | 203 | — |
| 8 | — | — | 169 | 132 |
| 15 | — | 160 | 161 | 93 |
| 35 | ND | ND | NA | 95 |
| CLcr (ml/h/kg) | ||||
| 1 | 87 | 88 | 88 | 94 |
| 8 | 79 | 91 | 88 | 93 |
| 15 | 85 | 92 | 94 | 82 |
| 35 | ND | ND | 84 | 92 |
a
The AUC is shown for days 1 and 8 (AUC0–α for day 35); t1/2, half-life of terminal elimination phase; CL/F, apparent oral clearance; CLrenal/F, apparent renal clearance; CLcr, calculated creatinine clearance based on ideal body weight.
b
—, not reported due to insufficient data.
c
Fed administration (day 8) was significantly different from fasted administration (day 1) (P<0.05).
d
Steady-state pharmacokinetics (day 15 or 35) were significantly different from first-dose pharmacokinetics (day 8) (P < 0.05).
e
ND, not determined on this visit.