Table 1.
Pharmacokinetic parameters for elosulfase alfa 2.0 mg/kg/QW or 2/0 mg/kg/QOW in patients with Morquio A syndrome
| Parameter | Elosulfase alfa 2.0 mg/kg/QOW | Elosulfase alfa 2.0 mg/kg/QW | Ratio of Elosulfase alfa QOW/QWa (%) |
|---|---|---|---|
| Week 0 | |||
| n | 24 | 22 | |
| AUC 0–∞, ng·min/mL | 287,597 (96,432.1), 14 | 231,074 (103,207.4), 15 | 124.5 |
| AUClast, ng·min/mL | 248,720 (97,063.7), 24 | 237,884 (100,328.6), 22 | 104.6 |
| C max, ng/mL | 1,438 (435.3), 24 | 1,494 (534.1), 22 | 96.2 |
| CL, mL/min/kg | 7.54 (2.002), 14 | 10.04 (3.733), 15 | 75.1 |
| V ss, mL/kg | 219.42 (95.483), 12 | 395.74 (315.636), 14 | 55.4 |
| V z, mL/kg | 68.79 (34.008), 14 | 123.66 (144.115), 15 | 55.6 |
| t ½, min | 6.57 (3.110), 14 | 7.52 (5.484), 15 | 87.4 |
| t max, min | 150 (58.1), 24 | 172 (75.3), 22 | 87.2 |
| Week 22 | |||
| n | 23 | 22 | |
| AUC 0–∞, ng·min/mL | 463,460 (491,418.9), 19 | 619,080 (422,048.3), 20 | 74.9 |
| AUClast, ng·min/mL | 411,687 (420,279.7), 23 | 577,371 (416,316.6), 22 | 71.3 |
| Cmax, ng/mL | 2,616 (2,702.1), 23 | 4,036 (3,237.1), 22 | 64.8 |
| CL, mL/min/kg | 6.50 (2.942), 19 | 7.08 (12.997), 20 | 91.8 |
| V ss, mL/kg | 245.19 (273.145), 17 | 649.67 (1,841.703), 20 | 37.7 |
| V z, mL/kg | 120.11 (71.076), 19 | 299.52 (543.309), 20 | 40.1 |
| t ½, min | 19.25 (19.217), 19 | 35.86 (21.485), 20 | 53.7 |
| t max, min | 159 (60.6), 23 | 202 (90.8), 22 | 78.5 |
| Week 22/Week 0b (%) | |||
| n | 23 | 21 | |
| AUC 0–∞, ng·min/mL | 179.2 | 328.6 | |
| AUClast, ng·min/mL | 176.3 | 280.6 | |
| C max, ng/mL | 183.6 | 291.6 | |
| CL, mL/min/kg | 87.0 | 46.4 | |
| V ss, mL/kg | 127.0 | 188.9 | |
| V z, mL/kg | 147.0 | 246.0 | |
| t ½, min | 280.0 | 696.0 | |
| t max, min | 119.8 | 145.7 | |
Values are expressed as mean (SD), n unless otherwise indicated
For patients who have missing values of AUC0–∞, t ½, CL, V z and V ss, the parameters could not be estimated due to insufficient data in the terminal phase of the plasma profile. For patients who have missing values of V ss only, their V ss was not reported due to a negative value. Adjusting for infusion caused a negative MRTinf value. The V ss value was also negative because of the relationship: V ss = MRTinf·CL
AUC 0–∞ area under the plasma concentration–time curve from time zero to infinity, AUC last area under the plasma concentration–time curve from time zero to the time of last measurable concentration, CL total clearance of drug after intravenous administration, C max observed maximum plasma concentration, MRTinf mean residence time extrapolated to infinity, SD standard deviation, QOW every other week, QW weekly, V ss apparent volume of distribution at steady-state, V z apparent volume of distribution based upon the terminal phase, t ½ elimination half-life
a Ratio is ratio of means
b Only patients with pharmacokinetic data available for both visits are included