Search: onr:"swepub:oai:DiVA.org:uu-134969" >
A model of hyperten...
A model of hypertension and proteinuria in cancer patients treated with the anti-angiogenic drug E7080
-
- Keizer, Ron J. (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri
-
Gupta, Anubha (author)
-
Mac Gillavry, Melvin R. (author)
-
show more...
-
Jansen, Mendel (author)
-
Wanders, Jantien (author)
-
Beijnen, Jos H. (author)
-
Schellens, Jan H. M. (author)
-
- Karlsson, Mats O. (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri
-
Huitema, Alwin D. R. (author)
-
show less...
-
(creator_code:org_t)
- 2010-07-23
- 2010
- English.
-
In: Journal of Pharmacokinetics and Pharmacodynamics. - : Springer Science and Business Media LLC. - 1567-567X .- 1573-8744. ; 37:4, s. 347-363
- Related links:
-
https://link.springe...
-
show more...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- 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.
Keyword
- Hypertension
- Proteinuria
- VEGF
- Pharmacodynamics
- Model
- PHARMACY
- FARMACI
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database