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Model-Based Analysi...
Model-Based Analysis Reveals a Sustained and Dose-Dependent Acceleration of Wound Healing by VEGF-A mRNA (AZD8601)
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- Almquist, Joachim (author)
- AstraZeneca, Sweden; Fraunhofer Chalmers Ctr, Sweden; AstraZeneca, Sweden
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- Rikard, S. Michaela (author)
- Univ Virginia, VA USA
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- Wagberg, Maria (author)
- AstraZeneca, Sweden
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- Bruce, Anthony C. (author)
- Univ Virginia, VA USA
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- Gennemark, Peter (author)
- Linköpings universitet,Avdelningen för medicinsk teknik,Tekniska fakulteten,AstraZeneca, Sweden
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- Fritsche-Danielson, Regina (author)
- AstraZeneca, Sweden
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- Chien, Kenneth R. (author)
- Karolinska Institutet,Karolinska Inst, Sweden
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- Peirce, Shayn M. (author)
- Univ Virginia, VA USA
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- Hansson, Kenny (author)
- AstraZeneca, Sweden
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- Lundahl, Anna (author)
- AstraZeneca, Sweden
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(creator_code:org_t)
- 2020-07-05
- 2020
- English.
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In: CPT. - : WILEY. - 2163-8306. ; 9:7, s. 384-394
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Abstract
Subject headings
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- Intradermal delivery of AZD8601, an mRNA designed to produce vascular endothelial growth factor A (VEGF-A), has previously been shown to accelerate cutaneous wound healing in a murine diabetic model. Here, we develop population pharmacokinetic and pharmacodynamic models aiming to quantify the effect of AZD8601 injections on the dynamics of wound healing. A dataset of 584 open wound area measurements from 131 mice was integrated from 3 independent studies encompassing different doses, dosing timepoints, and number of doses. Evaluation of several candidate models showed that wound healing acceleration is not likely driven directly by time-dependent VEGF-A concentration. Instead, we found that administration of AZD8601 induced a sustained acceleration of wound healing depending on the accumulated dose, with a dose producing 50% of the maximal effect of 92 mu g. Simulations with this model showed that a single dose of 200 mu g AZD8601 can reduce the time to reach 50% wound healing by up to 5 days.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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