Plasma mycophenolic acid and MPAG kinetic parameters for naive and adenovirus-infected Gunn rats after a single mycophenolic acid administration
Mycophenolic acid (80 mg/kg) was administered i.p., and blood samples were collected at 0.25, 0.5, 1, 1.5, 2, 4, 6, and 8 h after dosing. Plasma mycophenolic acid and MPAG concentrations were determined, and the various kinetic parameters shown were calculated using WinNonLin (noncompartmental model). Each value representative of three rats ± S.E.
Pharmacokinetic Parameters | HD Gunn | ID Gunn | LD Gunn | Control j/+ | Gunn |
|---|---|---|---|---|---|
| 0.26 OD260 U | 0.13 OD260 U | 0.065 OD260 U | 0.26 OD260 U | Uninfected | |
| AUCMPA,0-8 h (μg/ml/h) | 477 ± 60*** | 568 ± 156*** | 808 ± 16 | 442 ± 59*** | 1041 ± 210 |
| AUCMPA,4-8 h (μg/ml/h) | 216 ± 18 | 240 ± 62 | 325 ± 16 | 165 ± 19 | 374 ± 106 |
| Cmax (μg/ml) | 213 ± 30*** | 205 ± 32*** | 254 ± 18*** | 231 ± 34*** | 359 ± 10 |
| Tmax (μg/ml) | 15 ± 0 | 15 ± 0 | 15 ± 0 | 15 ± 0 | 20 ± 8 |
| t1/2,α (h) | 0.71 ± 0.11† | 1.06 ± 0.13‡ | 1.31 ± 0.15 | 0.53 ± 0.01 | 1.55 ± 0.18‡ |
| CL/F | 0.41 ± 0.07*** | 0.30 ± 0.06*** | 0.16 ± 0.01 | 0.35 ± 0.05*** | 0.11 ± 0.02 |
| V/F | 0.40 ± 0.04 | 0.46 ± 0.11 | 0.30 ± 0.02 | 0.26 ± 0.05 | 0.26 ± 0.05 |
| AUCMPAG,0-8 h (μg/ml/h) | 323 ± 24***‡ | 171 ± 11*** | 94 ± 11***‡ | 183 ± 10*** | 22 ± 3 |
| Cmax (μg/ml) | 199 ± 41***‡ | 100 ± 8 | 65 ± 8 | 46 ± 7 | 18 ± 3 |
| Tmax (μg/ml) | 30 ± 0 | 40 ± 10 | 60 ± 0 | 110 ± 66 | 60 ± 0 |
| AUCMPA/AUCMPAG | 1.4 | 3.2 | 8.2 | 2.7 | 44.9 |
AUCMPA, mycophenolic acid area under the plasma concentration-time curve; Cmax, peak plasma concentration; t1/2,α, plasma elimination half-life-alpha; Tmax, mean peak time; MPAG area under the plasma concentration-time curve.
↵*** p < 0.001 as compared with j/j.
↵† p < 0.05 as compared with j/j.
↵‡ p < 0.001 as compared with j/+.