Clinical Pharmacokinetics and Mass Balance of Veliparib in Combination with Temozolomide in Subjects with Nonhematologic Malignancies

Clinical Pharmacokinetics
Silpa NuthalapatiHao Xiong

Abstract

Veliparib is an orally active potent poly(ADP-ribose) polymerase (PARP) inhibitor currently in phase III clinical trials in solid tumors. This phase I study evaluated the pharmacokinetics and mass balance of veliparib administered alone and in combination with temozolomide, and assessed any potential pharmacokinetic drug-drug interaction between veliparib and temozolomide. This was an open-label, dose-escalation study of veliparib in combination with temozolomide in 42 subjects with nonhematologic malignancies. Veliparib was administered orally at doses ranging from 10 to 80 mg twice daily on days 1-7, and temozolomide was administered orally at 150-200 mg/m2 once daily on days 1-5 of each 28-day cycle. The pharmacokinetics of veliparib, its M8 metabolite, and temozolomide, as well as urinary excretion of unchanged veliparib and its M8 metabolite, were determined. Mean veliparib maximum observed plasma concentration (C max) and area under the plasma concentration-time curve for the first 6 h postdose (AUC6) values increased dose proportionally in the veliparib 10-80 mg twice-daily dose range. The urinary recovery of veliparib dose as the unchanged parent compound alone and together with the M8 metabolite was 73 ± 18 and 90 ± 22...Continue Reading

References

Sep 1, 1991·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·G de MurciaV Schreiber
Jun 15, 1995·Statistics in Medicine·S N GoodmanS Piantadosi
Apr 29, 1998·Cancer Chemotherapy and Pharmacology·S PiantadosiS Grossman
Apr 12, 2002·The Journal of Biological Chemistry·Valérie SchreiberGilbert de Murcia
Sep 2, 2004·Nature Genetics·Ronald A DePinho, Kornelia Polyak
May 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Cherrie K DonawhoDavid J Frost
Aug 12, 2008·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Robert A PariseJan H Beumer
Mar 26, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Xiaofeng LiYanbin Lao
Aug 25, 2012·Nature Reviews. Cancer·Peter Bouwman, Jos Jonkers
Nov 3, 2012·Cancer Research·Junko MuraiYves Pommier
Jul 25, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yuqiao ShenAlan Ashworth
Jun 21, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jing LiPatricia LoRusso
Feb 5, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Patricia M LoRussoGeoffrey I Shapiro

❮ Previous
Next ❯

Citations

Feb 17, 2017·Journal of Adolescent and Young Adult Oncology·Angela DautiAntoinette Anazodo
Oct 25, 2017·Clinical Pharmacokinetics·Jill J J GeenenJan H M Schellens
Oct 19, 2019·Targeted Oncology·Esha SachdevMonica M Mita
Oct 18, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Florence AtrafiAntonio Calles
Dec 15, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Rhys GillmanLionel Hebbard
Jul 27, 2021·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·David E KozonoEverett E Vokes
Aug 28, 2021·Biomedicines·Abdullah AlhusainiNiamh Lynam-Lennon

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.