Compartmental pharmacokinetic analysis of rituximab CSF concentrations in cynomolgus monkeys
| Parameter . | Parameter estimates for experiment no. 4 (1 monkey)* . | Parameter estimates from mean concentration profile across all experiments (nos. 4-7)* . |
|---|---|---|
| AUC, μg × h/mL | 4630 (455) | 3130 (492) |
| Cmax, μg/mL† | 2250 (503) | 2250 (1120) |
| Clearance, mL/h | 1.08 (0.106) | 1.60 (0.251) |
| V1, mL | 2.09 (0.493) | 1.96 (1.09) |
| Vss, mL | 4.41 (0.641) | 6.82 (1.88) |
| Initial half-life, h | 0.879 (0.216) | 0.414 (0.209) |
| Terminal half-life, h | 5.65 (0.367) | 4.96 (0.344) |
| MRT, h | 4.08 (0.403) | 4.28 (0.634) |
| Parameter . | Parameter estimates for experiment no. 4 (1 monkey)* . | Parameter estimates from mean concentration profile across all experiments (nos. 4-7)* . |
|---|---|---|
| AUC, μg × h/mL | 4630 (455) | 3130 (492) |
| Cmax, μg/mL† | 2250 (503) | 2250 (1120) |
| Clearance, mL/h | 1.08 (0.106) | 1.60 (0.251) |
| V1, mL | 2.09 (0.493) | 1.96 (1.09) |
| Vss, mL | 4.41 (0.641) | 6.82 (1.88) |
| Initial half-life, h | 0.879 (0.216) | 0.414 (0.209) |
| Terminal half-life, h | 5.65 (0.367) | 4.96 (0.344) |
| MRT, h | 4.08 (0.403) | 4.28 (0.634) |
Concentrations were normalized to a dose of 5 mg. A 2-compartment model was fit to the data using WinNonlin software (Pharsight). For this regression, the Nelder-Mead convergence routine was used and each concentration was assigned a weighting factor inversely proportional to the square of the model-predicted concentration (1/Y2).16 The corresponding plots of dose-normalized and model-predicted concentrations are shown in Figure 1B-C.
AUC indicates area under the curve; V1, initial distribution volume; Vss, volume of distribution at steady state; and MRT, mean residence time.
Standard error of the parameter estimate from the nonlinear regression fit of the compartmental model to the data.
Maximum concentration predicted by the model assuming bolus administration.