12.3 Pharmacokinetics
The pharmacokinetic parameters of XYNTHA in 30 PTPs 12 to 60 years old, who received a single infusion of 50 IU/kg XYNTHA are summarized in Table 3.
In addition, 25 of the same subjects later received a single infusion of 50 IU/kg of XYNTHA for a 6-month follow-up pharmacokinetic study. The parameters were comparable between baseline and 6 months, indicating no time-dependent changes in the pharmacokinetics of XYNTHA.
In a separate study, 8 of 30 subjects at least 12 years old with hemophilia A undergoing elective major surgery received a single 50 IU/kg infusion of XYNTHA. The pharmacokinetic parameters in these subjects are also summarized in Table 3.
Table 3: Mean ± SD XYNTHA Pharmacokinetic Parameters in Previously Treated Patients with Hemophilia A after Single 50 IU/kg DoseParameter | Initial Visit (n = 30) | Month 6 (n = 25) | Pre-surgery (n=8) |
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Abbreviations: AUC∞ = area under the plasma concentration-time curve from zero to infinity; Cmax = peak concentration; t1/2 = plasma elimination half-life; CL = clearance; n = number of subjects; SD = standard deviation; Vss = volume of distribution at steady-state. |
|
Cmax (IU/mL) | 1.08 ± 0.22 | 1.24 ± 0.42 | 1.08 ± 0.24 |
AUC∞ (IU∙hr/mL) | 13.5 ± 5.6 | 15.0 ± 7.5 | 16.0 ± 5.2 |
t1/2 (hr) | 11.2 ± 5.0 | 11.8 ± 6.2* | 16.7 ± 5.4 |
CL (mL/hr/kg) | 4.51 ± 2.23 | 4.04 ± 1.87 | 3.48 ± 1.25 |
Vss (mL/kg) | 66.1 ± 33.0 | 67.4 ± 32.6 | 69.0 ± 20.1 |
Recovery (IU/dL per IU/kg) | 2.15 ± 0.44 | 2.47 ± 0.84 | 2.17 ± 0.47 |
Table 4 shows the pharmacokinetic parameters of nine children; four aged 14 or 15 years of age, who are also included in the summary for the adults above, along with five children aged 3.7–5.8 years after single 50 IU/kg doses of XYNTHA. Compared to adults, the half-life of XYNTHA is shorter in children and the clearance (based on per kg body weight) is approximately 40% higher in children.
Table 4: Mean ± SD XYNTHA Pharmacokinetic Parameters in Previously Treated Pediatric Patients with Hemophilia A after Single 50 IU/kg DoseParameter | Young Children (n=5) | Adolescents (n=4) |
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Abbreviations: AUC∞ = area under the plasma concentration-time curve from zero to infinity; Cmax = peak concentration; t1/2 = plasma elimination half-life; CL = clearance; n = number of subjects; SD = standard deviation; Vss = volume of distribution at steady-state. |
Age (min - max, yr)) | 3.7 – 5.8 | 14 – 15 |
Cmax (IU/mL) | 0.78 ± 0.34 | 0.97 ± 0.21 |
AUC∞ (IU∙hr/mL) | 12.2 ± 6.50 | 8.5 ± 4.0 |
t1/2 (hr) | 8.3 ± 2.7 | 6.9 ± 2.4 |
CL (mL/hr/kg) | 6.29 ± 4.87 | 6.62 ± 2.16 |
Vss (mL/kg) | 66.9 ± 55.6 | 67.1 ± 13.6 |
Recovery (IU/dL per IU/kg) | 1.52 ± 0.69 | 1.95 ± 0.41 |