Table 3.
Probability of target attainment of oseltamivir carboxylate exposures in plasma following a range of oseltamivir dosing and automated peritoneal dialysis regimens simulated for 1000 patients
| Exposure variable | Urinary clearance | Dosing regimen | Probability of target attainment* | |||
|---|---|---|---|---|---|---|
| Initial simulation | CAPD only† | Intermediate APD‡ | Intensive APD§ | |||
| Plasma AUC0–120 | Anuric | 75 mg single dose | 1.000 | 1.000 | 1.000 | 1.000 |
| 60 mg single dose | 1.000 | 1.000 | 1.000 | 1.000 | ||
| 45 mg single dose | 1.000 | 1.000 | 1.000 | 1.000 | ||
| 30 mg single dose | 0.973 | 0.984 | 0.977 | 0.976 | ||
| Low urine¶ | 75 mg single dose | 1.000 | 1.000 | 1.000 | 1.000 | |
| 60 mg single dose | 1.000 | 1.000 | 1.000 | 1.000 | ||
| 45 mg single dose | 0.998 | 1.000 | 0.999 | 0.994 | ||
| 30 mg single dose | 0.773 | 0.818 | 0.784 | 0.759 | ||
| High urine** | 75 mg single dose | 0.194 | 0.199 | 0.195 | 0.190 | |
| 60 mg single dose | 0.035 | 0.044 | 0.040 | 0.040 | ||
| 45 mg single dose | 0.000 | 0.002 | 0.002 | 0.001 | ||
| 30 mg single dose | 0.000 | 0.000 | 0.000 | 0.000 | ||
| 75 mg (0 and 48 h) | 0.957 | – | – | – | ||
| 30 mg (five daily doses) | 0.913 | – | – | – | ||
| Plasma C120 | Anuric | 75 mg single dose | 0.974 | 0.980 | 0.978 | 0.966 |
| 60 mg single dose | 0.957 | 0.970 | 0.960 | 0.948 | ||
| 45 mg single dose | 0.929 | 0.940 | 0.917 | 0.904 | ||
| 30 mg single dose | 0.773 | 0.812 | 0.714 | 0.727 | ||
| Low urine¶ | 75 mg single dose | 0.674 | 0.700 | 0.668 | 0.649 | |
| 60 mg single dose | 0.547 | 0.591 | 0.544 | 0.515 | ||
| 45 mg single dose | 0.348 | 0.408 | 0.383 | 0.307 | ||
| 30 mg single dose | 0.065 | 0.080 | 0.072 | 0.053 | ||
| High urine** | 75 mg single dose | 0.000 | 0.000 | 0.000 | 0.000 | |
| 60 mg single dose | 0.000 | 0.000 | 0.000 | 0.000 | ||
| 45 mg single dose | 0.000 | 0.000 | 0.000 | 0.000 | ||
| 30 mg single dose | 0.000 | 0.000 | 0.000 | 0.000 | ||
| 75 mg (0 and 48 h) | 0.043 | – | – | – | ||
| 30 mg (five daily doses) | 0.905 | – | – | – | ||
Abbreviations are as follows: APD, automated peritoneal dialysis; AUC0–120, area under the concentration–time curve from time 0 to 120 h postdose; BSV, between-subject variability; C120, plasma concentration at 120 h postdose; CAPD, continuous ambulatory peritoneal dialysis; CCPD, continuous cycler-assisted peritoneal dialysis.
Proportion of simulated patients (n = 1000) achieving AUC0–120 of 31 820 ng h ml−1 or C120 of 170 ng ml−1.
Three CAPD sessions over 15 h during the day, followed by a single exchange of 9 h overnight.
A single CAPD exchange over 10 h before a 2 h break during the day, and three CCPD sessions over 9 h followed by a 3 h break overnight.
Three CCPD sessions over 8 h during the day, and two CAPD exchanges of 16 h overnight.
Simulated using a median urinary clearance of 0.289 l h−1 (70 kg)−1 (BSV 45%), calculated from the individual estimates [0.195 and 0.382 l h−1 (70 kg)−1] from patients 1 and 3.
Simulated using a median urinary clearance of 2.50 l h−1 (70 kg)−1 (BSV 10%), calculated from the individual estimates [2.43 and 2.58 l h−1 (70 kg)−1] from patients 6 and 10.