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A model of hyperten...
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Keizer, Ron J.Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri
(författare)
A model of hypertension and proteinuria in cancer patients treated with the anti-angiogenic drug E7080
- Artikel/kapitelEngelska2010
Förlag, utgivningsår, omfång ...
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2010-07-23
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Springer Science and Business Media LLC,2010
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-134969
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-134969URI
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https://doi.org/10.1007/s10928-010-9164-2DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Hypertension and proteinuria are commonly observed side-effects for anti-angiogenic drugs targeting the VEGF pathway. In most cases, hypertension can be controlled by prescription of anti-hypertensive (AH) therapy, while proteinuria often requires dose reductions or dose delays. We aimed to construct a pharmacokinetic-pharmacodynamic (PK-PD) model for hypertension and proteinuria following treatment with the experimental VEGF-inhibitor E7080, which would allow optimization of treatment, by assessing the influence of anti-hypertensive medication and dose reduction or dose delays in treating and avoiding toxicity. Data was collected from a phase I study of E7080 (n = 67), an inhibitor of multiple tyrosine kinases, among which VEGF. Blood pressure and urinalysis data were recorded weekly. Modeling was performed in NONMEM, and direct and indirect response PK-PD models were evaluated. A previously developed PK model was used. An indirect response PK-PD model described the increase in BP best, while the probability of developing proteinuria toxicity in response to exposure to E7080, was best described by a Markov transition model. This model may guide clinical interventions and provide treatment recommendations for E7080, and may serve as a template model for other drugs in this class.
Ämnesord och genrebeteckningar
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Hypertension
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Proteinuria
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VEGF
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Pharmacodynamics
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Model
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PHARMACY
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FARMACI
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Gupta, Anubha
(författare)
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Mac Gillavry, Melvin R.
(författare)
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Jansen, Mendel
(författare)
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Wanders, Jantien
(författare)
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Beijnen, Jos H.
(författare)
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Schellens, Jan H. M.
(författare)
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Karlsson, Mats O.Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri(Swepub:uu)matskarl
(författare)
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Huitema, Alwin D. R.
(författare)
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Uppsala universitetInstitutionen för farmaceutisk biovetenskap
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of Pharmacokinetics and Pharmacodynamics: Springer Science and Business Media LLC37:4, s. 347-3631567-567X1573-8744
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