TABLE 4.
Pharmacokinetic parameters and bioequivalence of l-AMT and l/d-AMT in humans with psoriasis given the same l-enantiomer dose
l-AMT and l/d-AMT were orally administered to 21 human subjects with psoriasis as described under Materials and Methods. Plasma samples were collected over a 12-h period and analyzed by LC-MS/MS. Pharmacokinetic parameters were derived from concentration vs. time profiles. There was no detectable d-isomer in the plasma after dosing of either drug product; values shown are only for the l-isomer in plasma. l-AMT was bioequivalent to l/d-AMT (i.e., 90% CI value between 0.8 and 1.25 for Cmax, AUC(0–12 h), and AUC∞). Values are mean ± S.D. (n = 21).
| l-AMT | l/d-AMT | 90% CI of the Ratio | |
|---|---|---|---|
| l dose, mg/kg | 0.01 ± 0.002 | 0.01 ± 0.002 | |
| d dose, mg/kg | 0.004 ± 0.001 | ||
| Cmax, nM | 74 ± 29 | 73 ± 28 | 0.82–1.07 |
| AUC(0–12 h), nM × h | 218 ± 70 | 202 ± 57 | 0.84–0.98 |
| AUC∞, nM × h | 238 ± 78 | 217 ± 61 | 0.82–0.97 |
| Tmax, h | 1.12 ± 0.63 | 0.81 ± 0.30 | |
| t1/2, h | 3.7 ± 0.8 | 3.7 ± 0.8 | |
| CL/kg, l/h/kg | 0.093 ± 0.026 | 0.099 ± 0.025 | |
| GFR/kg, l/h/kg | 0.094 ± 0.021 | 0.094 ± 0.021 | |
| VD/kg, l/kg | 0.48 ± 0.13 | 0.52 ± 0.15 |