Pharmacokinetics of Efmoroctocog alfa by Two-Compartment Model Highlights Hemophilia A Patients with Biphasic Decay, Long Mean Residence Time, and Beta Half-Life
Abstract
:1. Introduction
2. Subjects and Methods
2.1. Blood Collection and PK Design
2.2. PK Methods and Statistical Analysis
3. Results
3.1. PK Parameters Obtained by NCA, OCM, and TCM
3.2. OSA vs. CSA
3.3. SHL-rFVIII vs. rFVIIIFc PK Analysis
3.4. Analysis According to Blood Groups
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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(a) | ||||||||||||
AUC | AUMC | Cmax | IVR | MRT | Lambda_z HL | K1_0 HL | Cl | Vss | AUC_%Extrap | |||
N | Uxh/dL | Uxh2/dL | IU/dL | IU/dL/IU/kg | h | h | h | mL/h/kg | mL/kg | % | ||
NCA | 173 | Mean | 1978 | 39,793 | 94.46 | 2.22 | 19.09 | 17.27 | 2.36 | 55.08 | 3.23 | |
1 SD | 790 | 23,400 | 32.65 | 0.58 | 4.78 | 5.85 | 0.95 | 34.41 | 3.00 | |||
OCM | 173 | Mean | 1817 | 40,811 | 92.11 | 20.16 | 13.98 | 2.76 | 49.04 | |||
1SD | 819 | 31,764 | 30.59 | 7.15 | 4.95 | 1.28 | 12.77 | |||||
TCM | Alpha HL (h) | Beta_HL (h) | CLD2 (mL/h/kg) | |||||||||
106 | Mean | 1870 | 51,790 | 99.74 | 3.74 | 25.64 | 20.42 | 13.72 | 2.50 | 59.32 | 4.82 | |
1SD | 758 | 38,647 | 41.01 | 3.00 | 7.61 | 7.73 | 4.68 | 1.07 | 18.93 | 1.78 | ||
(b) | ||||||||||||
Non-Compartmental Analysis | ||||||||||||
AUC | AUMC | Cmax | MRT | Lambda_z HL | Cl | Vss | ||||||
Groups | N | Uxh/dL | Uxh2/dL | IU/dL | h | h | mL/h/kg | mL/kg | ||||
A | 106 | Mean | 1884 | 39,461 | 92.88 | 19.94 | 18.87 | 2.36 | 61.08 | |||
1 SD | 699 | 21,740 | 32.77 | 4.43 | 5.88 | 0.99 | 27.65 | |||||
B | 67 | Mean | 2072 | 40,616 | 101.65 | 18.11 | 15.88 | 2.41 | 52.30 | |||
1 SD | 907 | 26,696 | 38.42 | 5.32 | 6.51 | 0.96 | 26.01 |
Groups | N | Mean | Variance | Variance between Groups | F | p | |
---|---|---|---|---|---|---|---|
AUC (Uxh/dL) | NCA | 106 | 1884 | 488,274 | 2,509,245 | 2.40 | 0.09 |
OCM | 106 | 1689 | 502,411 | ||||
TCM | 106 | 1870 | 574,613 | ||||
AUMC (Uxh2/dL) | NCA | 106 | 39,461 | 472,632,451 | 13,903,028,009 | 7.67 | 0.006 |
OCM | 106 | 36,530 | 752,738,949 | ||||
TCM | 106 | 51,790 | 1,493,605,408 | ||||
Cmax (IU/dL) | NCA | 106 | 92.88 | 1074 | 5922 | 2.44 | 0.09 |
OCM | 106 | 89.34 | 892 | ||||
TCM | 106 | 99.74 | 1681 | ||||
Clearance (mL/h/kg) | NCA | 106 | 2.36 | 0.01 | 0.13 | 4.88 | 0.008 |
OCM | 106 | 2.84 | 0.02 | ||||
TCM | 106 | 2.50 | 0.01 | ||||
Vss (mL/kg) | NCA | 106 | 61.08 | 7.64 | 92.90 | 10.60 | 0.003 |
OCM | 106 | 48.84 | 1.86 | ||||
TCM | 106 | 59.32 | 3.58 | ||||
HL (h) | Lambda_z HL | 106 | 18.87 | 34.60 | 2804 | 34.50 | 0.0001 |
K 1-0 HL | 106 | 13.54 | 23.02 | ||||
Beta HL | 106 | 20.42 | 64.33 | ||||
MRT (h) | NCA | 106 | 19.94 | 19.64 | 2467 | 29.51 | 0.0003 |
OCM | 106 | 19.54 | 47.91 | ||||
TCM | 106 | 25.64 | 57.83 |
AUC | AUMC | Cmax | IVR | MRT | Lambda_z HL | K1_0 HL | Cl | Vss | AUC_Extrap | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
N | Uxh/dL | Uxh2/dL | IU/dL | IU/dL/IU/kg | h | h | h | mL/h2/kg | mL/kg | % | |||
NCA | OSA | 52 | Mean | 2149 | 44,699 | 101.05 | 2.12 | 19.46 | 17.24 | 2.51 | 58.01 | 3.29 | |
1 SD | 851 | 27,388 | 25.65 | 0.52 | 4.54 | 6.36 | 1.05 | 26.13 | 2.80 | ||||
CHA | 52 | Mean | 2265 | 43,162 | 116.36 | 2.44 | 18.09 | 16.98 | 2.37 | 54.96 | 4.92 | ||
1 SD | 889 | 26,148 | 29.36 | 0.61 | 4.48 | 7.95 | 1.04 | 31.19 | 3.21 | ||||
OCM | OSA | 52 | Mean | 2007 | 46,396 | 98.32 | 20.15 | 13.96 | 2.90 | 51.24 | |||
1 SD | 943 | 39,457 | 24.18 | 7.12 | 4.93 | 1.32 | 12.46 | ||||||
CHA | 52 | Mean | 2052 | 41,083 | 114.57 | 17.76 | 12.31 | 2.87 | 44.76 | ||||
1 SD | 946 | 33,013 | 28.52 | 6.18 | 4.28 | 1.50 | 42.92 | ||||||
TCM | Alpha HL (h) | Beta HL (h) | CLD2 (mL/h2/kg) | ||||||||||
OSA | 34 | Mean | 2169 | 61,128 | 123.24 | 3.01 | 25.43 | 19.23 | 13.19 | 2.60 | 59.98 | 5.42 | |
1 SD | 988 | 48,174 | 63.13 | 2.31 | 7.92 | 7.06 | 5.32 | 1.21 | 20.64 | 1.50 | |||
CHA | 34 | Mean | 2226 | 59,307 | 120.29 | 4.23 | 24.24 | 24.26 | 12.60 | 2.53 | 56.13 | 5.90 | |
1 SD | 1041 | 45,966 | 31.17 | 3.68 | 7.28 | 8.30 | 3.93 | 1.30 | 21.31 | 1.70 |
AUC | AUMC | Cmax | In Vivo Recovery | MRT | Lambda_z HL | K10_HL | Cl | Vss | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
N | Uxh/dL | Uxh2/dL | IU/Dl | IU/dL/IU/kg | h | h | h | mL/h/kg | mL/kg | |||
NCA | SHL rFVIII | 50 | Mean | 1320 | 20,877 | 76.84 | 2.33 | 15.09 | 17.33 | 2.83 | 63.82 | |
1 SD | 669 | 14,414 | 27.43 | 0.69 | 4.73 | 11.46 | 1.17 | 36.55 | ||||
Elocta | 50 | Mean | 1808 | 39,134 | 76.21 | 2.19 | 20.85 | 20.20 | 2.03 | 56.22 | ||
1 SD | 630 | 21,129 | 21.32 | 0.48 | 4.78 | 9.30 | 0.58 | 25.91 | ||||
OCM | SHL rFVIII | 50 | Mean | 1159 | 19,231 | 76.36 | 15.17 | 10.52 | 3.44 | 47.72 | ||
1 SD | 596 | 15,848 | 27.06 | 4.56 | 3.16 | 1.80 | 15.52 | |||||
Elocta | 50 | Mean | 1710 | 41,685 | 76.68 | 22.79 | 15.80 | 2.31 | 49.18 | |||
1 SD | 641 | 25,664 | 21.79 | 6.71 | 4.65 | 0.76 | 12.09 | |||||
Alpha HL (h) | Beta HL (h) | |||||||||||
TCM | SHL rFVIII | 32 | Mean | 1287 | 34,292 | 75.90 | 3.78 | 24.16 | 20.98 | 11.77 | 6.35 | 141.21 |
1 SD | 572 | 26,928 | 23.28 | 2.21 | 9.90 | 10.04 | 3.36 | 1.82 | 33.91 | |||
Elocta | 32 | Mean | 1846 | 63,636 | 79.80 | 3.59 | 29.55 | 22.6 | 15.97 | 4.63 | 126.13 | |
1 SD | 882 | 79,504 | 21.13 | 2.49 | 11.98 | 12.78 | 4.55 | 1.31 | 17.50 |
N | FVIII:C IU/dL (Mean + 1 SD) | Student’s t-Paired Test | ||
---|---|---|---|---|
Trough at 48 h | SHL rFVIII FVIII | 15 | 2.16 ± 1.77 | p = 0.0003 |
Efmoroctocog alfa | 15 | 7.87 ± 3.57 | ||
Trough at 72 h | SHL rFVIII FVIII | 24 | 2.78 ± 1.01 | p = 0.004 |
Efmoroctocog alfa | 24 | 4.99 ± 3.24 | ||
Trough at 96 h | SHL rFVIII FVIII | 11 | 2.35 ± 1.10 | p = 0.05 |
Efmoroctocog alfa | 11 | 4.01 ± 2.18 |
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Morfini, M.; Peyvandi, F.; Mancuso, M.E.; Marchesini, E.; Tagliaferri, A.; Gualtierotti, R.; Castaman, G.; Pollio, B.; Santoro, C.; Banov, L.; et al. Pharmacokinetics of Efmoroctocog alfa by Two-Compartment Model Highlights Hemophilia A Patients with Biphasic Decay, Long Mean Residence Time, and Beta Half-Life. J. Clin. Med. 2024, 13, 4986. https://doi.org/10.3390/jcm13174986
Morfini M, Peyvandi F, Mancuso ME, Marchesini E, Tagliaferri A, Gualtierotti R, Castaman G, Pollio B, Santoro C, Banov L, et al. Pharmacokinetics of Efmoroctocog alfa by Two-Compartment Model Highlights Hemophilia A Patients with Biphasic Decay, Long Mean Residence Time, and Beta Half-Life. Journal of Clinical Medicine. 2024; 13(17):4986. https://doi.org/10.3390/jcm13174986
Chicago/Turabian StyleMorfini, Massimo, Flora Peyvandi, Maria Elisa Mancuso, Emanuela Marchesini, Annarita Tagliaferri, Roberta Gualtierotti, Giancarlo Castaman, Berardino Pollio, Cristina Santoro, Luisa Banov, and et al. 2024. "Pharmacokinetics of Efmoroctocog alfa by Two-Compartment Model Highlights Hemophilia A Patients with Biphasic Decay, Long Mean Residence Time, and Beta Half-Life" Journal of Clinical Medicine 13, no. 17: 4986. https://doi.org/10.3390/jcm13174986