SynthesisEuropean journal of clinical pharmacology2012
Prediction of drug clearance in a smoking population: modeling the impact of variable cigarette consumption on the induction of CYP1A2.
Synthesis in European journal of clinical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Seeing what is behind the smokescreen: A systematic review of methodological aspects of smoking interaction studies over the last three decades and implications for future clinical trials.Clinical and translational science · 2023Pooled it
- Meta-analysis: the effects of smoking on the disposition of two commonly used antipsychotic agents, olanzapine and clozapine.BMJ open · 2014Pooled it
- Understanding Pharmacokinetic Variability of Pomalidomide: A Physiologically Based Pharmacokinetic Analysis of Disease-Related Physiology, Ethnicity, Hepatic Impairment, Food Effects, Drug Interactions, and Smoking.Clinical pharmacokinetics · 2026Article
- Integrating Population Approaches With Physiologically Based Pharmacokinetic Models: A Novel Framework for Parameter Estimation.CPT: pharmacometrics & systems pharmacology · 2026Article
- Physiologically Based Pharmacokinetic (PBPK) Model to Predict the Magnitude of Drug-Drug Interaction Between Fezolinetant and CYP1A2 Inhibitors.Journal of clinical pharmacology · 2025Article
- Virtual twins for model-informed precision dosing of clozapine in patients with treatment-resistant schizophrenia.CPT: pharmacometrics & systems pharmacology · 2024Article
- Therapeutic drug monitoring as an essential tool to ensure clozapine efficacy and prevent its toxicity in smokers: a case report.European journal of clinical pharmacology · 2023Article
- Delineating gene-environment effects using virtual twins of patients treated with clozapine.CPT: pharmacometrics & systems pharmacology · 2023Article
- Physiologically based pharmacokinetic (PBPK) modeling of flurbiprofen in different CYP2C9 genotypes.Archives of pharmacal research · 2022Article
- Causal relationship from coffee consumption to diseases and mortality: a review of observational and Mendelian randomization studies including cardiometabolic diseases, cancer, gallstones and other diseases.European journal of nutrition · 2022Review
- Population pharmacokinetic and exposure-response analysis of apremilast in Japanese subjects with moderate to severe psoriasis.The Journal of dermatology · 2021Article
- Sex-dependent dynamics of metabolism in primary mouse hepatocytes.Archives of toxicology · 2021Article
- Using physiologically-based pharmacokinetic modeling for predicting the effects of hepatic impairment on the pharmacokinetics of olanzapine and samidorphan given as a combination tablet.CPT: pharmacometrics & systems pharmacology · 2021Article
- Loxapine in patient with clozapine-resistant psychosis.The mental health clinician · 2021Article
- Therapeutic Drug Monitoring of Second- and Third-Generation Antipsychotic Drugs-Influence of Smoking Behavior and Inflammation on Pharmacokinetics.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Associations of coffee and tea consumption with lung cancer risk.International journal of cancer · 2021Article
- Cigarette smoking enhances the metabolic activation of the polycyclic aromatic hydrocarbon phenanthrene in humans.Carcinogenesis · 2021Article
- Coffee consumption and risk of bladder cancer: a pooled analysis of 501,604 participants from 12 cohort studies in the BLadder Cancer Epidemiology and Nutritional Determinants (BLEND) international study.European journal of epidemiology · 2020Article
- Utilizing physiologically based pharmacokinetic modeling to predict theoretically conceivable extreme elevation of serum flecainide concentration in an anuric hemodialysis patient with cirrhosis.European journal of clinical pharmacology · 2020Article
- Physiologically-Based Pharmacokinetic Modeling for Predicting Drug Interactions of a Combination of Olanzapine and Samidorphan.CPT: pharmacometrics & systems pharmacology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo derive estimates of CYP1A2 abundance as a function of daily cigarette consumption and use these values to predict the clearances of CYP1A2 substrates in smokers.
methodsSmoking-induced changes in hepatic CYP1A2 abundance were extrapolated from reported in vivo caffeine clearance data for sub-groups of a smoking population that were categorized according to their daily cigarette consumption. These abundance values together with in vitro-in vivo extrapolation (IVIVE) within the Simcyp population-based Simulator were used to predict the clearances of caffeine, theophylline, and clozapine in smokers. The model was used subsequently to predict differences in oral clearance between smoker and non-smoker cohorts in a Phase 1 clinical trial involving PF-2400013, a drug metabolized by CYP1A2.
resultsEstimated hepatic CYP1A2 abundance values were 52, 64, 79, 90, and 94 pmol/mg microsomal protein for subjects smoking 0, 1-5, 6-10, 11-20, and >20 cigarettes/day respectively. Predicted -fold increases in oral clearance of caffeine, theophylline and clozapine in smokers relative to non-smokers were consistent with observed data. The validated model was able to recover the smoking-induced increase in oral clearance of PF-2400013; predicted and observed mean (CV%) values in male nonsmokers and smokers were 90 L/h (40%) and 141 L/h (34%) respectively, and 100 L/h (58%) and 131 L/h (33%) respectively.
conclusionsThis study demonstrates that it may be possible to predict the clearance of CYP1A2 substrates in smoking populations using quantitative estimates of CYP1A2 abundance based on daily cigarette consumption in conjunction with an IVIVE approach.
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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.