Trial reportClinical pharmacokinetics2014
Pharmacokinetic evaluations of the co-administrations of vandetanib and metformin, digoxin, midazolam, omeprazole or ranitidine.
Trial report in Clinical pharmacokinetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 4 registered trials, which are not on this map. Cited by 23 papers.
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.
A Phase I, Randomized, Open-label, Single-center Study to Assess the Pharmacokinetics of Vandetanib (CAPRELSA) in Healthy Subjects When a Single Oral Dose of Vandetanib 300 mg is Administered Alone and in Combination With Omeprazole or Ranitidine
A Phase I, Open-label, Single-center Study to Assess the Pharmacokinetics of Midazolam, a CYP3A4 Substrate, in Healthy Subjects When Administered Alone and in Combination With a Single Dose of 800-mg Vandetanib (CAPRELSA)
A Phase I, Open-label, Single-center Study to Assess the Pharmacokinetics of Metformin, an OCT2 Substrate, in Healthy Subjects When Administered Alone and in Combination With a Single Oral Dose of Vandetanib (CAPRELSA) 800 mg
A Phase I, Open-label, Single-center Study to Assess the Pharmacokinetics of Digoxin in Healthy Subjects When Administered Alone and in Combination With a Single Dose of Vandetanib (CAPRELSA) 300 mg
Who cites it
23 citing papers in PubMed, 61 citations in OpenAlex.
- Drug-drug interaction of cefiderocol, a siderophore cephalosporin, via human drug transporters.European journal of clinical pharmacology · 2018Trial
- Effects of Cimetidine and Dolutegravir on the Endogenous Drug-Drug Interaction Biomarkers for Organic Cation Transporter 2 and Multidrug and Toxin Extrusion Protein 1 in Healthy Volunteers.Clinical pharmacology and therapeutics · 2025Article
- Pretreatment and analysis techniques development of TKIs in biological samples for pharmacokinetic studies and therapeutic drug monitoring.Journal of pharmaceutical analysis · 2024Review
- Bidirectional pharmacokinetic drug interactions between olaparib and metformin.Cancer chemotherapy and pharmacology · 2024Article
- Drug Repurposing for Targeting Myeloid-Derived Suppressor-Cell-Generated Immunosuppression in Ovarian Cancer: A Literature Review of Potential Candidates.Pharmaceutics · 2023Review
- Recent Advances in Visible-Light Photoredox Catalysis for the Thiol-Ene/Yne Reactions.Molecules (Basel, Switzerland) · 2022Review
- Proton Pump Inhibitors and Cancer: Current State of Play.Frontiers in pharmacology · 2022Review
- In silico Analysis of Publicly Available Transcriptomics Data Identifies Putative Prognostic and Therapeutic Molecular Targets for Papillary Thyroid Carcinoma.International journal of general medicine · 2022Article
- Article
- Article
- Proton Pump Inhibitors and Oncologic Treatment Efficacy: A Practical Review of the Literature for Oncologists.Current oncology (Toronto, Ont.) · 2021Review
- Pharmacokinetic Interaction between Sorafenib and Atorvastatin, and Sorafenib and Metformin in Rats.Pharmaceutics · 2020Article
- Physiologically-Based Pharmacokinetic Modeling Analysis for Quantitative Prediction of Renal Transporter-Mediated Interactions Between Metformin and Cimetidine.CPT: pharmacometrics & systems pharmacology · 2019Article
- Interaction between phytotherapy and oral anticancer agents: prospective study and literature review.Medical oncology (Northwood, London, England) · 2019Review
- A Generic Model for Quantitative Prediction of Interactions Mediated by Efflux Transporters and Cytochromes: Application to P-Glycoprotein and Cytochrome 3A4.Clinical pharmacokinetics · 2019Article
- Clinically relevant drug interactions with multikinase inhibitors: a review.Therapeutic advances in medical oncology · 2019Review
- Pharmacokinetics of metformin in patients with gastrointestinal intolerance.Diabetes, obesity & metabolism · 2018Article
- Pharmacodynamic and Pharmacokinetic Markers For Anti-angiogenic Cancer Therapy: Implications for Dosing and Selection of Patients.European journal of drug metabolism and pharmacokinetics · 2018Review
- Drug Interactions of Metformin Involving Drug Transporter Proteins.Advanced pharmaceutical bulletin · 2017Review
- Renal Drug Transporters and Drug Interactions.Clinical pharmacokinetics · 2017Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveVandetanib is a selective inhibitor of vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR) and rearranged during transfection (RET) signalling, indicated for the treatment of medullary thyroid cancer. We investigated potential drug-drug interactions between vandetanib and metformin [organic cation transporter 2 (OCT2) substrate; NCT01551615]; digoxin [P-glycoprotein (P-gp) substrate; NCT01561781]; midazolam [cytochrome P450 (CYP) 3A4 substrate; NCT01544140]; omeprazole (proton pump inhibitor) or ranitidine (histamine H2-receptor antagonist; both NCT01539655).
methodsFour open-label, phase I studies were conducted in healthy volunteers: n = 14 (metformin), n = 14 (digoxin), n = 17 (midazolam), n = 16 (omeprazole), n = 18 (ranitidine). Three of these comprised the following regimens: metformin 1000 mg ± vandetanib 800 mg, midazolam 7.5 mg ± vandetanib 800 mg, or digoxin 0.25 mg ± vandetanib 300 mg. The randomized study comprised vandetanib 300 mg alone and then either (i) omeprazole 40 mg (days 1-4), and omeprazole + vandetanib (day 5); or (ii) ranitidine 150 mg (day 1), and ranitidine + vandetanib (day 2). The primary objective assessed metformin, digoxin, midazolam and vandetanib pharmacokinetics.
resultsVandetanib + metformin increased metformin area under the plasma concentration-time curve from zero to infinity (AUC0-∞) and maximum observed plasma concentration (Cmax) by 74 and 50 %, respectively, and decreased the geometric mean metformin renal clearance (CLR) by 52 % versus metformin alone. Vandetanib + digoxin increased digoxin area under the concentration-time curve from zero to the last quantifiable concentration (AUC0-last) and Cmax by 23 and 29 %, respectively, versus digoxin alone, with only a 9 % decrease in CLR. Vandetanib had no effect on midazolam exposure. Vandetanib exposure was unchanged during co-administration with omeprazole/ranitidine. Treatment combinations were generally well tolerated.
conclusionPatients receiving vandetanib with metformin/digoxin may require additional monitoring of metformin/digoxin, with dose adjustments where necessary. Vandetanib with CYP3A4 substrates or omeprazole/ranitidine is unlikely to result in clinically relevant drug-drug interactions.
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What OpenQuestion holds
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.