TABLE 1.
METH and AMP metabolite pharmacokinetics in timed-pregnant Sprague-Dawley rats after an intravenous bolus dose of 1 mg/kg METH on GD7 or GD21
Pharmacokinetic parameters were determined from model-independent analyses of the METH serum concentration versus time profiles.
| METH | GD7 | GD21 |
|---|---|---|
| AUC (ng-min/ml) | 17,997 ± 1489 | 24,445 ± 4477c |
| t1/2λz (min) | 91 ± 16a | 115 ± 6a,c |
| MRT (min) | 95 ± 3 | 157 ± 19c |
| Vd (l/kg) | 7 ± 1 | 7 ± 1 |
| Vdss (l/kg) | 5 ± 0.3 | 6 ± 1 |
| ClT (ml · min−1 · kg−1) | 55 ± 5 | 39 ± 6c |
| ClR (ml · min−1 · kg−1) | 6 ± 1 | 3 ± 1c |
| ClNR (ml · min−1 · kg−1) | 50 ± 5 | 36 ± 5c |
| METH dose in urine (%) | 10 ± 3 | 8 ± 2 |
| AMP metabolite | ||
| AUC (ng-min/ml) | 3459 ± 926 | 7025 ± 1625c |
| t1/2λz (min) | 95 ± 12a | 189 ± 11a,c,d |
| Tmax (min) | 72 ± 27 | 156 ± 49c |
| Cmax (ng/ml) | 16 ± 4 | 22 ± 4c |
| AMP dose in urine (%) | 2 ± 0.4 | 3 ± 0.6 |
| Molar ratio of AMP/METH AUCb | 0.21 ± 0.05 | 0.31 ± 0.03c |
a
Harmonic mean and pseudo S.D. (Lam et al., 1985).
b
The molar ratio of AMP/METH AUC was achieved by dividing the nmol/ml per hour AMP AUC value by the nmol/ml per hour METH AUC value.
c
p < 0.05 when compared to GD7 values.
d
p < 0.05 when compared to METH values on GD21.