Table 4.
PK parameters and ammonia at steady state dosing with sodium phenylbutyrate and glycerol phenylbutyrate (Study days 7 and 14).
| PK/PD parameters | Glycerol phenylbutyrate (n = 11) | NaPBA (n = 11) |
|---|---|---|
| PBA in plasma mean (CV%) | ||
| AUC0–24 (μg·h/mL) | 631 (44.9) | 236 (105.2) |
| Cmaxss (μg/mL) | 95.6 (42.0) | 37.4 (101.6) |
| Cminss (μg/mL) | 1.50 (99.8) | 0.366 (171.3) |
| PAA in plasma mean (CV%) | ||
| AUC0–24 (μg·h/mL) | 964 (63.6) | 773 (73.3) |
| Cmaxss (μg/mL) | 90.5 (69.1) | 75.1 (64.4) |
| Cminss (μg/mL) | 2.99 (122.1) | 0.674 (130.5) |
| PAGN in plasma mean (CV%) | ||
| AUC0–24 (μg·h/mL) | 1378 (40.2) | 1015 (44.7) |
| Cmaxss (μg/mL) | 105 (33.5) | 74.8 (37.3) |
| Cminss (μg/mL) | 13.1 (64.9) | 4.63 (66.4) |
| PAGN in urine mean (CV%) | ||
| Total excreted 0–24 h (g) | 12.5 (56.9) | 12.5 (51.3) |
| Recovery of PBA as PAGN (%) Fe0–24 (%) | 66.4 (23.9) | 69.0 (23.9) |
| Ammonia mean (SD) | ||
| AUC (μmol/L) | 603.8 (187.92) | 814.6 (322.36) |
| Cmaxss (μmol/L) | 47.77 (12.800) | 55.66 (21.607) |
| Total number (%) of ammonia values above ULN* | 24 (31.6) | 14 (18.4) |
| Diet | ||
| Actual protein intake (g/d) Mean (SD) | 23.98 (9.891) | 24.35 (12.445) |
| Actual protein intake (g/kg/d) Mean (SD) | 0.61 (0.16) | 0.64 (0.35) |
| Judged compliant with diet (days 7, 14) | 8/11 (72.7%) | 9/11 (81.8%) |
| Difference in ammonia between GPB and NaPBA | ||
| Mean difference of AUC (μmol/L) (SD) | −210.8 (310.89) | |
| Ratio of Geometric means | 0.781 | |
| 90% Confidence interval | (0.609, 1.002) | |
| 95% Confidence interval | (0.575, 1.061) | |
AUC0–24: Area under the concentration from time 0 (pre-dose) to 24 h, Cmaxss:Maximum plasma concentration at steady state, Cminss: Minimum plasma concentration at steady state, CV% – coefficient of variation.
*
% abnormal ammonia values presented as mean (SD); the denominator is the total number of ammonia values at all time points (76).