Table 1.
Mean pharmacokinetic parameters for NTBC, mesotrione and tyrosine.
a) NTBC (mean (n = 10) ± s.d.)
| Dose (mg kg–1) | Cmax (µg ml−1) | tmax (h) | AUC (µg ml−1 h) Compartmental | AUC (µg ml−1 h) Non-compartmental | t½ (h) |
|---|---|---|---|---|---|
| 1 (capsule) | 7.81 ± 1.17 | 1.5–4 | 599 ± 153 | 602 ± 154 | 54.5 ± 13.0 |
| 1 (solution) | 8.19 ± 1.04 | 0.25–3.5 | 598 ± 142 | 602 ± 146 | 53.6 ± 8.2 |
| Parameter | Differences in formulations | Westlake's 95% interval | Non-parametric bioequivalence evaluation | ||
|---|---|---|---|---|---|
| AUC1 | P = 0.99 | 92.4 to 107.6% | 94.5 to 105.6% | ||
| AUC2 | P = 0.99 | 93.1 to 106.9% | 95.4 to 105.9% | ||
| t1/2 | P = 0.78 | 87.5 to 112.5% | 90.8 to 109.1% | ||
| Cmax | P = 0.023 | 77.4 to 122.6% | 102.6 to 124.3% | ||
| Cmax/AUC | P = 0.002 | 81.3 to 118.7% | 105.2 to 121.5% | ||
| b) mesotrione (mean (n = 6) ± s.d.) | ||||
|---|---|---|---|---|
| Dose (mg kg−1) | Cmax (µg ml−1) | tmax (h) | AUC (µg ml−1 h) | t½ (h) |
| 0.1 | 0.09 ± 0.05 | 1 | 0.15 ± 0.06 | 0.9 ± 0.3 |
| 0.5 | 0.58 ± 0.23 | 1–3 | 1.08 ± 0.26 | 1.3 ± 0.5 |
| 4 | 3.93 ± 1.85 | 1–6 | 8.50 ± 1.11 | 0.9 ± 0.2 |
| c) tyrosine AUC (nmol ml−1 h) values measured from 72 h prior to dosing to 72 h post dosing | |||||
|---|---|---|---|---|---|
| Dose of mesotrione (mg kg−1) 0.1 | 0.5 | 4 | |||
| Post dose | Mean | 5871 | 6246 | 10026 | |
| s.d. | 927 | 145 | 1227 | ||
| Adjusted for pre-dose | 6095 | 6751 | 9298 | ||
| P value vs 0.1 mg kg−1 | 0.21 (NS) | < 0.01** | |||
| P value vs 0.5 mg kg−1 | <0.01** | ||||
1
Non-compartmental analysis
2
Compartmental analysis.
NS not significant
**
statistically significant difference at the 1% level.