Trial reportClinical pharmacokinetics2020
Pharmacokinetic Drug-Drug Interaction of Apalutamide, Part 1: Clinical Studies in Healthy Men and Patients with Castration-Resistant Prostate Cancer.
Trial report in Clinical pharmacokinetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Safety profile of darolutamide versus placebo: a systematic review and meta-analysis.Prostate cancer and prostatic diseases · 2024Pooled it
- Pharmacokinetics and Use-Testing of Apalutamide Prepared in Aqueous Food Vehicles for Alternative Administration.Clinical pharmacology in drug development · 2021Trial
- Sustained Drug-Drug Interaction Between Cyclosporine and Apalutamide in a Patient With Metastatic Hormone-Sensitive Prostate Cancer: A Case Report and Evaluation of CYP3A4 Induction via Pregnane X Receptor Activation by Apalutamide.Case reports in oncological medicine · 2026Article
- Relugolix in Combination with Androgen Receptor Pathway Inhibitors in the Treatment of Metastatic Prostate Cancer: A Clinical Perspective.Targeted oncology · 2025Review
- Liquid chromatography-tandem mass spectrometry assay for the simultaneous determination of apalutamide and its active metabolite N-desmethyl apalutamide, and its application in real-world patients with castration-resistant prostate cancer.Frontiers in pharmacology · 2025Article
- Concomitant Administration of Psychotropic and Prostate Cancer Drugs: A Pharmacoepidemiologic Study Using Drug-Drug Interaction Databases.Biomedicines · 2024Article
- Pharmacokinetic Interactions Between Abiraterone, Apalutamide, Darolutamide or Enzalutamide and Antithrombotic Drugs: Prediction of Clinical Events and Review of Pharmacological Information.Cardiovascular drugs and therapy · 2024Review
- A practical assessment protocol for clinically relevant P-glycoprotein-mediated drug-drug interactions.Frontiers in pharmacology · 2024Article
- Can Mechanistic Static Models for Drug-Drug Interactions Support Regulatory Filing for Study Waivers and Label Recommendations?Clinical pharmacokinetics · 2023Review
- Alternatives to rifampicin: A review and perspectives on the choice of strong CYP3A inducers for clinical drug-drug interaction studies.Clinical and translational science · 2022Review
- New Oral Antitumor Drugs and Medication Safety in Uro-Oncology: Implications for Clinical Practice Based on a Subgroup Analysis of the AMBORA Trial.Journal of clinical medicine · 2022Article
- Drug Interactions Affecting Oral Anticoagulant Use.Circulation. Arrhythmia and electrophysiology · 2022Review
- Review
- Treatment Landscape for Patients with Castration-Resistant Prostate Cancer: Patient Selection and Unmet Clinical Needs.Research and reports in urology · 2022Review
- The role of pregnane X receptor (PXR) in substance metabolism.Frontiers in endocrinology · 2022Review
- Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE).Cancer chemotherapy and pharmacology · 2021Article
- Novel Treatment Strategy Using Second-Generation Androgen Receptor Inhibitors for Non-Metastatic Castration-Resistant Prostate Cancer.Biomedicines · 2021Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesTwo phase I studies assessed the drug-drug interaction potential of apalutamide as a substrate and perpetrator.
methodsStudy A randomized 45 healthy men to single-dose apalutamide 240 mg alone or with strong inhibitors of cytochrome P450 (CYP)3A4 (itraconazole) or CYP2C8 (gemfibrozil). In study B, 23 patients with castration-resistant prostate cancer received probes for CYP3A4 (midazolam), CYP2C9 (warfarin), CYP2C19 (omeprazole), and CYP2C8 (pioglitazone), and transporter substrates for P-glycoprotein (P-gp) (fexofenadine) and breast cancer resistance protein (BCRP)/organic anion transporting polypeptide (OATP) 1B1 (rosuvastatin) at baseline and after repeat once-daily administration of apalutamide 240 mg to steady state.
resultsSystemic exposure (area under the plasma concentration-time curve) to single-dose apalutamide increased 68% with gemfibrozil but was relatively unchanged with itraconazole (study A). Apalutamide reduced systemic exposure to midazolam ↓92%, omeprazole ↓85%, S-warfarin ↓46%, fexofenadine ↓30%, rosuvastatin ↓41%, and pioglitazone ↓18% (study B). After a single dose, apalutamide is predominantly metabolized by CYP2C8, and less by CYP3A4.
conclusionsCo-administration of apalutamide with CYP3A4, CYP2C19, CYP2C9, P-gp, BCRP or OATP1B1 substrates may cause loss of activity for these medications. Therefore, appropriate mitigation strategies are recommended.
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Registered trials
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 OpenQuestion graph.