dose (mg/kg) Number of rats that died  concentration (μM) ratio  (juvenile/mature) *e ratio (died/surviving)
mature rats (estimated) *a juvenile rats
alive *b all *c died *d Plasma brain plasma brain
plasma brain plasma brain plasma brain plasma brain alive died alive died
300 1 11.0 1.2 136 34 159 40.9 1509 416 12 137 29 346 11 12
500 3 18.4 2.0 186 52 265 68.2 1732 365 10 94 26 182 9 7
600 5 22.1 2.5 225 45 318 81.9 1316 474 10 60 18 190 6 11
700 12 25.8 2.9 266 60 371 95.5 778 234 10 30 21 81 3 4
850 33 31.3 3.5 292 56 451 116.0 573 162 9 18 16 46 2 3
1000 40 36.8 4.1 275 47 530 136.5 647 177 8 18 11 43 2 4
"*a: Plasma and brain concentration in mature rats for each dose group are estimated based on the concentration of the 1000 mg/kg group, which was proportionally allotted for dose *b: Plasma and brain concentration of surviving rats are the averages of two rats *c: Calculated average for all animals including surviving and deceased *d: Calculated average for deceased only *e: Note that proportionality of juvenile/mature ratio breaks down for deceased rats. The reasons may include: (1) death occurred at a certain brain concentration level, making  further increase  impossible; (2) sampling methods may not have been adequate
Table 2: Estimated plasma and brain concentration (Cmax) of oseltamivir (as free base) for mature, surviving juvenile, and deceased juvenile rats, and juvenile/mature ratio by survival state (calculated using the data from post-marketing TK test [46,47]).