Table 4.
Mean (SD) Bayesian Pharmacokinetic Estimates for EZN-2208, SN38,and SN38G
| CL (L/h) |
V1 (L) |
Q1 (L/h) |
V2 (L) |
AUC Fraction α Phase |
AUC Fraction β Phase |
α Half-life (h) |
β Half-lifea (h) |
Elimination Half-lifea (h) |
|
|---|---|---|---|---|---|---|---|---|---|
| EZN-2208 | |||||||||
| Mean | 0.20 | 5.11 | 0.19 | 1.54 | 0.125 | 0.875 | 5.35 | 25.14 | 17.1 |
| SD | 0.063 | 1.94 | 0.20 | 0.56 | 0.062 | 0.062 | 1.95 | 2.20 | 2.79 |
| SN38 | |||||||||
| Mean | 21.1 | 625 | 9.4 | 205 | 0.56 | 0.44 | 14.2 | 73.8 | 20.7 |
| SD | 13.6 | 407 | 19.5 | 323 | 0.34 | 0.34 | 6.71 | 62.9 | 4.42 |
| SN38G | |||||||||
| Mean | 19.7 | 827 | 6.8 | 15017 | 0.69 | 0.31 | 21.9 | 2188 | 34.9 |
| SD | 13.4 | 448 | 3.3 | 12613 | 0.16 | 0.16 | 3.7 | 1523 | 18.2 |
Abbreviations: α, fast distribution phrase; AUC, area-under-the concentration curve; β, slow distribution phase; CL, elimination clearance; Q1, intercompartmental clearance; SD, standard deviation; SN38G = glucuronidated SN38; V1, central distribution volume; V2, peripheral distribution volume.
a
β half-life corresponds to the terminal slope for the plasma concentration decay. Elimination half-life describes the elimination of the drug from the organism, defined as V1*log(2)/CL.