Evidence map›Paper›PMID 36219340›Full record

ReviewClinical pharmacokinetics2022

Pharmacokinetics and Pharmacodynamics of PARP Inhibitors in Oncology.

Maaike A C Bruin, Gabe S Sonke, Jos H Beijnen, Alwin D R Huitema

Open access · hybridAbstract readReview
In one paragraph

Review in Clinical pharmacokinetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 1 pooled it
10.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

66 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.

  1. Pooled it
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  6. Current status of radionuclide therapy targeting PARP in cancer: challenges and prospects.European journal of nuclear medicine and molecular imaging · 2026
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6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Maaike A C BruinDepartment of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. ma.bruin@nki.nl.ORCID http://orcid.org/0000-0002-0300-8281
Gabe S SonkeDepartment of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Jos H BeijnenDepartment of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Alwin D R HuitemaDepartment of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
The Netherlands Cancer Institute · NLUtrecht University · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Olaparib, niraparib, rucaparib, and talazoparib are poly (ADP-ribose) polymerase (PARP) inhibitors approved for the treatment of ovarian, breast, pancreatic, and/or prostate cancer. Poly (ADP-ribose) polymerase inhibitors are potent inhibitors of the PARP enzymes with comparable half-maximal inhibitory concentrations in the nanomolar range. Olaparib and rucaparib are orally dosed twice a day, extensively metabolized by cytochrome P450 enzymes, and inhibitors of several enzymes and drug transporters with a high risk for drug-drug interactions. Niraparib and talazoparib are orally dosed once a day with a lower risk for niraparib and a minimal risk for talazoparib to cause drug-drug interactions. All four PARP inhibitors show moderate-to-high interindividual variability in plasma exposure. Higher exposure is associated with an increase in toxicity, mostly hematological toxicity. For talazoparib, exposure-efficacy relationships have been described, but for olaparib, niraparib, and rucaparib this relationship remains inconclusive. Further studies are required to investigate exposure-response relationships to improve dosing of PARP inhibitors, in which therapeutic drug monitoring could play an important role. In this review, we give an overview of the pharmacokinetic properties of the four PARP inhibitors, including considerations for patients with renal dysfunction or hepatic impairment, the effect of food, and drug-drug interactions. Furthermore, we focus on the pharmacodynamics and summarize the available exposure-efficacy and exposure-toxicity relationships.

Indexed as

Ovarian NeoplasmsPoly(ADP-ribose) Polymerase InhibitorsAdenosine DiphosphateFemaleHumansPoly(ADP-ribose) PolymerasesRiboseAdenosine DiphosphatePoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesRibose

Identifiers

PMID36219340
PMCPMC9734231
OpenAlexW4304182933

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.