Trial reportBritish journal of clinical pharmacology2006
Effects of cytochrome P450 3A modulators ketoconazole and carbamazepine on quetiapine pharmacokinetics.
Trial report in British journal of clinical pharmacology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 159 citations in OpenAlex.
- Effect of coadministered ketoconazole, a strong cytochrome P450 3A4 enzyme inhibitor, on the pharmacokinetics of ciclesonide and its active metabolite desisobutyryl-ciclesonide.Clinical pharmacokinetics · 2008Trial
- Possible clinical drug interactions between ticagrelor and concomitant medications: for adverse drug event monitoring in real-world.Cardiovascular drugs and therapy · 2026Article
- Therapeutic drug monitoring in children and adolescents treated with quetiapine for different psychiatric disorders: results of the TDM-VIGIL pharmacovigilance study.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- A Novel Workflow for Fast Elucidation of Drug Metabolites for Screening-Combining In Silico Metabolite Prediction With Trapped Ion Mobility QTOF-MS.Drug testing and analysis · 2026Article
- Serum concentrations of selective serotonin reuptake inhibitors and atypical antipsychotics in children and adolescents: data from routine clinical care.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- Article
- Evaluation the inhibitory effect of nicardipine on the metabolism of quetiapine.Frontiers in pharmacology · 2025Article
- Pharmacokinetic Prediction of Immediate- and Extended-Release Tablets for Patients with Liver Disease Using Whole Body Physiologically-Based Pharmacokinetic Modeling for the Antipsychotic Drug Quetiapine.AAPS PharmSciTech · 2024Article
- Acute Quetiapine Intoxication: Relationship Between Ingested Dose, Serum Concentration and Clinical Presentation-Structured Literature Review and Analysis.Journal of xenobiotics · 2024Review
- Dose-dependent effect of lamotrigine on quetiapine serum concentration in patients using instant release tablets.European journal of clinical pharmacology · 2024Article
- Post-therapy plasma concentrations of quetiapine in Taiwanese patients.Neuropsychopharmacology reports · 2023Article
- Pharmacokinetic Interactions Between Antiseizure and Psychiatric Medications.Current neuropharmacology · 2023Article
- 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
- Comparison of serum and whole blood concentrations in quetiapine overdose cases.Forensic toxicology · 2022Article
- Pharmacokinetics of caffeine self-administered in overdose in a Japanese patient admitted to hospital.Journal of pharmaceutical health care and sciences · 2021Article
- Severe Adverse Drug Reactions to Quetiapine in Two Patients CarryingInternational journal of molecular sciences · 2021Article
- Dose Adjustment of Quetiapine and Aripiprazole for Pregnant Women Using Physiologically Based Pharmacokinetic Modeling and Simulation.Clinical pharmacokinetics · 2021Article
- Pharmacokinetics of duloxetine self-administered in overdose with quetiapine and other antipsychotic drugs in a Japanese patient admitted to hospital.Journal of pharmaceutical health care and sciences · 2021Article
- Clinically Relevant Interactions between Atypical Antipsychotics and Anti-Infective Agents.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Prevalence and sort of pharmacokinetic drug-drug interactions in hospitalized psychiatric patients.Journal of neural transmission (Vienna, Austria : 1996) · 2020Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo explore the potential for drug interactions on quetiapine pharmacokinetics using in vitro and in vivo assessments.
methodsThe CYP enzymes responsible for quetiapine metabolite formation were assessed using recombinant expressed CYPs and CYP-selective inhibitors. P-glycoprotein (Pgp) transport was tested in MDCK cells expressing the human MDR1 gene. The effects of CYP3A4 inhibition were evaluated clinically in 12 healthy volunteers that received 25 mg quetiapine before and after 4 days of treatment with ketoconazole 200 mg daily. To assess CYP3A4 induction in vivo, 18 patients with psychiatric disorders were titrated to steady-state quetiapine levels (300 mg twice daily), then titrated to 600 mg daily carbamazepine for 2 weeks.
resultsCYP3A4 was found to be responsible for formation of quetiapine sulfoxide and N- and O-desalkylquetiapine and not a Pgp substrate. In the clinical studies, ketoconazole increased mean quetiapine plasma C(max) by 3.35-fold, from 45 to 150 ng ml(-1) (mean C(max) ratio 90% CI 2.51, 4.47) and decreased its clearance (Cl/F) by 84%, from 138 to 22 l h(-1) (mean ratio 90% CI 0.13, 0.20). Carbamazepine decreased quetiapine plasma C(max) by 80%, from 1042 to 205 ng ml(-1) (mean C(max) ratio 90% CI 0.14, 0.28) and increased its clearance 7.5-fold, from 65 to 483 l h(-1) (mean ratio 90% CI 6.04, 9.28).
conclusionsCytochrome P450 3A4 is a primary enzyme responsible for the metabolic clearance of quetiapine. Quetiapine pharmacokinetics were affected by concomitant administration of ketoconazole and carbamazepine, and therefore other drugs and ingested natural products that strongly modulate the activity or expression of CYP3A4 would be predicted to change exposure to quetiapine.
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