Table 1.
Pharmacokinetics of nelfinavir, M8, and nelfinavir plus M8 after once-daily administration of nelfinavir/ritonavir combinations for 14 days.*
| Values (geometric mean + range) | |||
|---|---|---|---|
| Parameter† | Group 1:nelfinavir/ritonavir2000/200 mg (n = 8) | Group 2:nelfinavir/ritonavir2000/400 mg (n = 8) | Group 3:nelfinavir/ritonavir2500/200 mg (n = 4) |
| Nelfinavir | |||
| AUC24h,corr (h.mg l−1) | 76.8 (32.4–121.3) | 51.3 (23.5–114.8) | 61.9 (48.1–89.3) |
| Cmax (mg l−1) | 7.2 (3.4–9.3) | 5.1 (2.9–9.4) | 6.7 (6.4–7.6) |
| Cmin (mg l−1) | 0.76 (0.28–2.1) | 0.43 (0.16–1.8) | 0.47 (0.18–1.8) |
| Tmax (h)‡ | 4.0 (2.5–5.0) | 4.6 (2.6–6.0) | 4.5 (3.0–5.0) |
| CL/F.kg (l.h.kg) | 0.35 (0.16–0.84) | 0.51 (0.24–0.95) | 0.52 (0.27–0.74) |
| Vd/F.kg (l kg−1) | 3.2 (1.8–5.4) | 4.5 (2.9–9.2) | 4.3 (3.6–5.0) |
| T1/2 (h) | 6.5 (4.4–11.3) | 6.1 (4.3–9.2) | 5.8 (4.0–9.1) |
| M8§ | |||
| AUC24h,corr (h.mg l−1) | 38.5 (21.5–57.7) | 40.9 (30.1–58.8) | 45.3 (30.0–63.4) |
| Cmax (mg l−1) | 3.4 (2.3–5.6) | 3.7 (2.8–4.9) | 4.3 (2.9–5.9) |
| Cmin (mg l−1) | 0.63 (0.46–1.1) | 0.59 (0.32–1.1) | 0.67 (0.35–1.7) |
| Tmax (h)‡ | 5.0 (4.0–5.0) | 5.0 (4.0–6.1) | 4.5 (4.0–5.0) |
| T1/2 (h) | 9.7 (7.5–13.6) | 8.6 (6.0–11.8) | 8.9 (7.4–13.3) |
| Nelfinavir + M8 | |||
| AUC24h,corr (h.mg l−1) | 116.4 (53.9–172.6) | 94.6 (61.6–173.7) | 108.3 (94.6–152.8) |
| Cmin (mg l−1) | 1.4 (0.81–3.2) | 1.1 (0.61–2.9) | 1.2 (0.77–3.5) |
| M8:nelfinavir ratio | |||
| Ratio for AUC24h,corr | 0.50 (0.32–0.75) | 0.80 (0.42–1.6) | 0.73 (0.46–0.98) |
| Ratio for Cmin | 0.83 (0.43–1.9) | 1.36 (0.50–4.3) | 1.43 (0.61–3.3) |
*
Pharmacokinetic parameters were assessed after intake of drugs with a full breakfast: 610 kcal, 33% fat, 16% proteins, 51% carbohydrates and 130 ml water (study day 15).
†
AUC24h,corr, Corrected 24 h area under the concentration–time curve (see text); Cmin, trough concentration at 24 h; Cmax, highest observed plasma concentration; tmax, sampling time for Cmax; CL/F.kg, total clearance corrected for weight; Vd/F.kg, volume of distribution corrected for weight; t1/2, elimination half-life; F, bioavailability.
‡
Median (and range).
§
CL/F.kg and Vd/F.kg can not be calculated for M8, as dose is unknown.