Table 5.
Pharmacokinetic Parametersa for Compound 32 Administered by Intravenous and Intraperitoneal Routes
| dose (mg kg−1) |
Cmax (ng mL−1) |
Tmax (h) |
AUC0-last (h ng mL−1) |
AUC0-∞ (h ng mL−1) |
t1/2 (h) | MRTlast (h) |
Vd (mL kg−1) |
Kel (1 h−1) |
F (%) |
Cl (mL h−1 kg−1) |
|---|---|---|---|---|---|---|---|---|---|---|
| 0.5, i.v. | 359 | 0.083 | 234 | 238 | 0.689 | 0.703 | 2090 | 1.01 | 100 | 2110 |
| 1.0, i.p. | 88.4 | 2.0 | 650 | 700 | 7.23 | 6.24 | 14,900 | 0.096 | 139 | 1430 |
| 3.0, i.p. | 315 | 2.0 | 2060 | 2120 | 4.68 | 5.68 | 9570 | 0.148 | 147 | 1420 |
| 10, i.p. | 786 | 4.0 | 4900 | 4920 | 2.98 | 5.02 | 8730 | 0.233 | 105 | 2030 |
a
In healthy adult male Wistar rats; with 3 per group. Dosing formulation: for i.v., DMSO/20% 2-hydroxypropyl-β-cyclodetrin (Sigma-Aldrich, 10:90); for i.p., DMSO/Kolliphor EL (Sigma-Aldrich)/PBS (15:15:70). Abbreviations: Cmax, maximal concentration; Tmax, time at which maximal concentration observed; AUC0-last, area under the plasma drug concentration–time curve up to the last quantifiable time point; AUC0-∞, area under the plasma drug concentration–time curve to infinite time; T1/2, terminal half-life; MRTlast, mean residence time; Vd, volume of distribution; Kel, elimination rate constant; F, biovailability; and Cl, total body clearance.