TABLE 3.
In vitro and in vivo pharmacokinetic properties of 844-TFM
| Pharmacokinetic propertya | Value |
|---|---|
| Solubility (μM) | |
| pH 2 | 446.5 |
| pH 7.4 | 390.0 |
| PAMPA, pH 7.4 | |
| Mean Pe (10−6cm/s) | 2.0 |
| LogPe | −5.7 |
| Mouse Hepatic Microsomes Stability (in vitro) | |
| kel (min−1) | 0.1 |
| t1/2 (min) | 5.2 |
| In vitro CLint (μl/min/mg protein) | 267.3 |
| CLint (ml/min/kg) | 1,052.4 |
| CLhepatic (ml/min/kg) | 82.9 |
| Mouse pharmacokinetic parameters (in vivo)b | |
| Intravenous administration | |
| AUC i.v. 5 mg/kg (h · ng/ml) | 5,627 (2,181) |
| elimination half-life (h) | 1.03 (0.17) |
| kel (h−1) | 0.69 (0.12) |
| V (liter/kg) | 0.811 (0.221) |
| Clearance (ml/kg · h) | 638 (231) |
| Other routes of administration | |
| AUC p.o. 25 mg/kg (ng · h/ml) | 58 (54) |
| AUC s.c. 25 mg/kg (ng · h/ml) | 1,168 (593) |
| p.o. bioavailability (%) | 0.15 (0.14) |
| s.c. bioavailability (%) | 3.0 (1.5) |
a
PAMPA, parallel artificial membrane permeability assay; Pe, effective permeability coefficient; kel, elimination rate constant; t1/2, half-life; CLint, intrinsic clearance; CLhepatic, hepatic clearance; AUC, area under the concentration-time curve; V, volume of distribution; i.v., intravenous; p.o., oral; s.c., subcutaneous.
b
Average (SD).