ArticleBritish journal of clinical pharmacology1999
Zolpidem metabolism in vitro: responsible cytochromes, chemical inhibitors, and in vivo correlations.
Article in British journal of clinical pharmacology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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.
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Who cites it
27 citing papers in PubMed, 131 citations in OpenAlex.
- CYP2D6 Genotype Phenotype Discordance Due to Drug-Drug Interaction.Clinical pharmacology and therapeutics · 2018Trial
- Pharmacokinetics of zolpidem from sublingual zolpidem tartrate tablets in healthy elderly versus non-elderly subjects.Drugs & aging · 2014Trial
- Effect of voriconazole on the pharmacokinetics and pharmacodynamics of zolpidem in healthy subjects.British journal of clinical pharmacology · 2007Trial
- Pharmacokinetic properties of zolpidem in elderly and young adults: possible modulation by testosterone in men.British journal of clinical pharmacology · 2003Trial
- Population Pharmacokinetic-Pharmacodynamic Analysis of Zolpidem in Healthy Volunteers: Covariate Contributions to Variability in CNS Responses.CPT: pharmacometrics & systems pharmacology · 2026Article
- PBBM Considerations for Base Models, Model Validation, and Application Steps: Workshop Summary Report.Molecular pharmaceutics · 2024Review
- Astronaut omics and the impact of space on the human body at scale.Nature communications · 2024Review
- Pharmacogenomics of Dementia: Personalizing the Treatment of Cognitive and Neuropsychiatric Symptoms.Genes · 2023Review
- 2-(4-Fluorophenyl)-1ACS chemical neuroscience · 2023Article
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Effect of CYP3A4 metabolism on sex differences in the pharmacokinetics and pharmacodynamics of zolpidem.Scientific reports · 2021Article
- Acute Hyponatremia Resulting from Duloxetine-induced Syndrome of Inappropriate Antidiuretic Hormone Secretion.Internal medicine (Tokyo, Japan) · 2019Article
- Interactions between antidepressants, sleep aids and selected breast cancer therapy.Mental illness · 2019Article
- Psychiatric Disorders and Oxidative Injury: Antioxidant Effects of Zolpidem Therapy disclosedComputational and structural biotechnology journal · 2019Article
- Putting Tuberculosis (TB) To Rest: Transformation of the Sleep Aid, Ambien, and "Anagrams" Generated Potent Antituberculosis Agents.ACS infectious diseases · 2015Article
- The behavioral pharmacology of zolpidem: evidence for the functional significance of α1-containing GABA(A) receptors.Psychopharmacology · 2014Review
- Comparative pharmacokinetics of zolpidem tartrate in five ethnic populations of China.Acta pharmaceutica Sinica. B · 2014Article
- Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect.Neuropsychiatric disease and treatment · 2014Review
- Pharmacokinetic interaction between zolpidem and ciprofloxacin in healthy volunteers.European journal of drug metabolism and pharmacokinetics · 2011Article
- In vitro-in vivo extrapolation of zolpidem as a perpetrator of metabolic interactions involving CYP3A.European journal of clinical pharmacology · 2010Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
aimsTo determine the human cytochromes mediating biotransformation of the imidazopyridine hypnotic, zolpidem, and the clinical correlates of the findings.
methodsKinetic properties of zolpidem biotransformation to its three hydroxylated metabolites were studied in vitro using human liver microsomes and heterologously expressed individual human cytochromes.
resultsThe metabolic product termed M-3 accounted for more than 80% of net intrinsic clearance by liver microsomes in vitro. Microsomes containing human cytochromes CYP1A2, 2C9, 2C19, 2D6, and 3 A4 expressed by cDNA-transfected human lymphoblastoid cells mediated zolpidem metabolism in vitro. The kinetic profile for zolpidem metabolite formation by each individual cytochrome was combined with estimated relative abundances based on immunological quantification, yielding projected contributions to net intrinsic clearance of: 61% for 3 A4, 22% for 2C9, 14% for 1A2, and less than 3% for 2D6 and 2C19. These values were consistent with inhibitory effects of ketoconazole and sulfaphenazole on zolpidem biotransformation by liver microsomes. Ketoconazole had a 50% inhibitory concentration (IC50 ) of 0.61 microm vs formation of the M-3 metabolite of zolpidem in vitro; in a clinical study, ketoconazole coadministration reduced zolpidem oral clearance by approximately 40%, somewhat less than anticipated based on the IC50 value and total plasma ketoconazole levels, but much more than predicted based on unbound plasma ketoconazole levels.
conclusionsThe incomplete dependence of zolpidem clearance on CYP3A activity has clinical implications for susceptibility to metabolic inhibition.
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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.