Factors contributing to the nonlinear pharmacokinetics of astegolimab : a close examination of potential causes
Aim: This paper describes a case study of an antibody therapeutic targeting a membrane-bound receptor, also present in systemic circulation, as a soluble receptor. During phase I studies of astegolimab, nonlinear pharmacokinetics (PKs) were observed. We investigated the potential contribution of antidrug antibodies, target-mediated drug disposition and assay format. Materials & methods: A more target-tolerant assay was developed, and a subset of phase I samples were evaluated in both free and total PK assay formats. Results & conclusion: Our results demonstrate that there were two main contributors to PK nonlinearity: soluble target interference in the free PK assay, in addition to target-mediated drug disposition. Antidrug antibody status did not significantly impact PK.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Bioanalysis - 15(2023), 21 vom: 04. Nov., Seite 1305-1314 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sperinde, Gizette [VerfasserIn] |
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| Links: |
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| Themen: |
27TW751DTH |
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| Anmerkungen: |
Date Completed 01.11.2023 Date Revised 01.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/bio-2023-0115 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM362854815 |
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| 100 | 1 | |a Sperinde, Gizette |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Factors contributing to the nonlinear pharmacokinetics of astegolimab |b a close examination of potential causes |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 01.11.2023 | ||
| 500 | |a Date Revised 01.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Aim: This paper describes a case study of an antibody therapeutic targeting a membrane-bound receptor, also present in systemic circulation, as a soluble receptor. During phase I studies of astegolimab, nonlinear pharmacokinetics (PKs) were observed. We investigated the potential contribution of antidrug antibodies, target-mediated drug disposition and assay format. Materials & methods: A more target-tolerant assay was developed, and a subset of phase I samples were evaluated in both free and total PK assay formats. Results & conclusion: Our results demonstrate that there were two main contributors to PK nonlinearity: soluble target interference in the free PK assay, in addition to target-mediated drug disposition. Antidrug antibody status did not significantly impact PK | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a free PK assay | |
| 650 | 4 | |a non-linear PK | |
| 650 | 4 | |a target-mediated drug disposition | |
| 650 | 4 | |a total PK assay | |
| 650 | 7 | |a astegolimab |2 NLM | |
| 650 | 7 | |a 27TW751DTH |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 700 | 1 | |a Dolton, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wenhui |e verfasserin |4 aut | |
| 700 | 1 | |a Mathews, Joel |e verfasserin |4 aut | |
| 700 | 1 | |a Putnam, Wendy |e verfasserin |4 aut | |
| 700 | 1 | |a Fischer, Saloumeh K |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:15 |g year:2023 |g number:21 |g day:04 |g month:11 |g pages:1305-1314 |
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