Table 2.
Serum concentration data (median and range) for HGA, tyrosine, and nitisinone in patients with AKU treated with nitisinone (N = 8 per dose group)
| Time | 1 mg | 2 mg | 4 mg | 8 mg | |
|---|---|---|---|---|---|
| Nitisinone | |||||
| C av (μmol/L) | Week 4 | 0.47 (0.3–0.8) | 1.04 (0.7–1.6) | 1.94 (1.3–2.6) | 5.49 (2.3–7.9) |
| C min (μmol/L) | Week 4 | 0.30 (<0.2–0.5) | 0.70 (0.5–1.2) | 1.40 (1.0–2.3) | 4.55 (1.5–6.2) |
| C max (μmol/L) | Week 4 | 0.70 (0.4–1.1) | 1.55 (0.9–1.9) | 2.50 (1.9–3.0) | 7.30 (3.3–9.7) |
| CL/F (mL/h·kg) | Week 4 | 2.80 (1.8–6.7) | 3.49 (1.7–4.6) | 3.49 (1.9–5.2) | 2.27 (1.6–5.0) |
| HGA | |||||
| C av (μmol/L) | Baseline | 32.96 (22.5–44.1) | 34.21 (25.1–29.1) | 37.69 (28.9–49.9) | 38.61 (25.2–47.7) |
| Week 4 | 3.93 (0.5–7.3) | 3.32 (<3.1–5.8) | <1.3 (<1.3–1.3) | <0.4 (<0.4–0.4) | |
| C max (μmol/L) | Baseline | 51.30 (40.8–69.9) | 52.85 (39.8–72.9) | 61.70 (48.4–88.3) | 57.05 (38.8–78.2) |
| Week 4 | 6.60 (4.3–10.7) | 5.10 (<3.1–7.5) | 3.40 (<3.1–4.7) | <3.1 (<3.1–3.2) | |
| Tyrosine | |||||
| C av (μmol/L) | Baseline | 56.0 (50–61) | 62.6 (46–79) | 58.0 (47–75) | 59.3 (50–82) |
| Week 4 | 667.3 (511–879) | 702.1 (596–948) | 805.9 (639–1,059) | 860.0 (627–970) | |
| C max (μmol/L) | Baseline | 71.0 (57–113) | 77.5 (59–100) | 80.5 (57–114) | 75.0 (62–120) |
| Week 4 | 721.0 (594–978) | 835.5 (662–1,010) | 889.0 (696–1,155) | 984.0 (715–1,066) | |
C av average serum concentration during the 24-hour dosing interval (C av = AUC24/24), C min minimum serum concentration, C max maximum serum concentration, CL/F oral clearance