A model of hypertension and proteinuria in cancer patients treated with the anti-angiogenic drug E7080.

Journal of Pharmacokinetics and Pharmacodynamics
Ron J KeizerA D R Huitema

Abstract

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 ser...Continue Reading

References

Mar 1, 1979·Clinical Pharmacology and Therapeutics·L B SheinerJ Ham
Aug 1, 1993·Journal of Pharmacokinetics and Biopharmaceutics·N L DaynekaW J Jusko
Oct 1, 1995·Australian and New Zealand Journal of Medicine·J A LeviH Wheeler
Apr 29, 2004·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·UNKNOWN Kidney Disease Outcomes Quality Initiative (K/DOQI)
Feb 1, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kathy D MillerHope S Rugo
Jul 19, 2005·Computer Methods and Programs in Biomedicine·Lars LindbomNiclas Jonsson
Feb 1, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Maria Luisa VeronesePeter J O'Dwyer
Nov 14, 2006·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Ferry A L M Eskens, Jaap Verweij
Jan 31, 2007·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Xiaolei ZhuChirag R Parikh
May 25, 2007·Nature Reviews. Cancer·Henk M W Verheul, Herbert M Pinedo
Jun 26, 2007·Annals of Oncology : Official Journal of the European Society for Medical Oncology·O RixeH Izzedine
Jan 4, 2008·The New England Journal of Medicine·Michel AziziStéphane Oudard
Mar 12, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Stefan Sleijfer, Erik Wiemer
May 1, 2008·Journal of Pharmacokinetics and Pharmacodynamics·Chantaratsamon DansirikulMats O Karlsson
Jun 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Neeltje SteeghsEelco de Koning
Oct 10, 2008·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M ScartozziS Cascinu
Mar 5, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kazuhiko YamadaTomohide Tamura
Oct 17, 2012·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Joseph A VassalottiLynda A Szczech

❮ Previous
Next ❯

Citations

Nov 28, 2012·Clinical Pharmacokinetics·Ines PauleMichel Tod
Jun 21, 2011·Journal of Thyroid Research·Karen GómezCamilo Jiménez
Feb 9, 2012·Current Oncology Reports·Gennaro DanieleJohann S de Bono
Jun 1, 2014·Journal of Pharmacological and Toxicological Methods·Antonello CarusoThierry Lavé
Nov 8, 2014·Investigational New Drugs·Anne-Charlotte DubbelmanJos H Beijnen
Oct 21, 2015·Expert Opinion on Drug Safety·Jolanta KrajewskaBarbara Jarzab
Oct 19, 2013·British Journal of Clinical Pharmacology·Brendan C BenderLena E Friberg
Feb 3, 2012·British Journal of Clinical Pharmacology·Ron J KeizerAlwin D R Huitema
Dec 7, 2013·CPT: Pharmacometrics & Systems Pharmacology·E K HanssonM O Karlsson
Oct 17, 2014·Expert Opinion on Pharmacotherapy·Jolanta Krajewska, Barbara Jarzab
Jul 28, 2012·Orvosi hetilap·Bálint AlaszticsSándor Valent
Feb 27, 2016·European Journal of Clinical Pharmacology·A H M de Vries SchultinkA D R Huitema
Feb 12, 2015·The New England Journal of Medicine·Martin SchlumbergerSteven I Sherman
Apr 5, 2018·Expert Opinion on Drug Metabolism & Toxicology·Stefano CavalieriSalvatore Alfieri
Oct 4, 2017·Expert Opinion on Drug Discovery·Silvia Maria LavezziItalo Poggesi
Jul 24, 2018·Cancer Control : Journal of the Moffitt Cancer Center·Koichi Suyama, Hirotaka Iwase
Feb 2, 2018·Medical Oncology·Koichi SuyamaHirotaka Iwase
Jan 27, 2019·CPT: Pharmacometrics & Systems Pharmacology·Ronald NiebeckerMats O Karlsson
Feb 24, 2016·Oncogenesis·P E Porporato
Mar 13, 2012·Pharmacological Reviews·E J Verspohl
Aug 28, 2020·Cancer Chemotherapy and Pharmacology·Eduard SchmulensonUlrich Jaehde
Nov 13, 2015·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Akihiko TsuruokaYasuhiro Funahashi
Jun 22, 2017·The AAPS Journal·Emilie Schindler, Mats O Karlsson
Mar 1, 2017·Expert Review of Endocrinology & Metabolism·Jolanta KrajewskaBarbara Jarzab
Jan 16, 2017·World Journal of Surgical Oncology·Morimasa KitamuraKoichi Omori
Jul 8, 2017·Molecular and Clinical Oncology·Koichi SuyamaHirotaka Iwase
Jul 15, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David S HongJohn Nemunaitis
Mar 5, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kazuhiko YamadaTomohide Tamura
Jan 21, 2021·CPT: Pharmacometrics & Systems Pharmacology·Yuki OtaniYusuke Tanigawara
May 30, 2021·Critical Reviews in Oncology/hematology·Stefano FogliRomano Danesi

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft

Software Mentioned

NONMEM
PsN

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Antihypertensive Agents: Mechanisms of Action

Antihypertensive drugs are used to treat hypertension (high blood pressure) which aims to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Discover the latest research on antihypertensive drugs and their mechanism of action here.

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.