ArticleScientific reports2019
Sex-, feeding-, and circadian time-dependency of P-glycoprotein expression and activity - implications for mechanistic pharmacokinetics modeling.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
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Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
- Sex and the Developmental Environment Shape Molecular Networks Underlying Bronchial Responsiveness in Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The intersection of circadian rhythms and the blood-brain barrier with drug efficacy and delivery in neurological disorders.Advanced drug delivery reviews · 2025Review
- The Circadian Rhythm Gene Network Could Distinguish Molecular Profile and Prognosis for Glioblastoma.International journal of molecular sciences · 2025Article
- Exploratory Study of Sex Differences in P-Glycoprotein Function at the Blood-Brain Barrier.Clinical and translational science · 2025Article
- Connecting the mechanisms of tumor sex differences with cancer therapy.Molecular and cellular biochemistry · 2024Review
- Recent Advances in Hepatic Metabolic Regulation by the Nuclear Factor Rev-erbɑ.Current drug metabolism · 2024Review
- Cardiac PET Imaging of ATP Binding Cassette (ABC) Transporters: Opportunities and Challenges.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Diurnal Changes in Capecitabine Clock-Controlled Metabolism Enzymes Are Responsible for Its Pharmacokinetics in Male Mice.Journal of biological rhythms · 2023Article
- Regulation of Circadian Genes Nr1d1 and Nr1d2 in Sex-Different Manners during Liver Aging.International journal of molecular sciences · 2022Article
- An Overview of the Circadian Clock in the Frame of Chronotherapy: From Bench to Bedside.Pharmaceutics · 2022Review
- Antidepressants and Circadian Rhythm: Exploring Their Bidirectional Interaction for the Treatment of Depression.Pharmaceutics · 2021Review
- Exploring the link between chronobiology and drug delivery: effects on cancer therapy.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Circadian Effects of Drug Responses.Annual review of biomedical engineering · 2021Article
- Sex disparities matter in cancer development and therapy.Nature reviews. Cancer · 2021Review
- Dose- and time-dependent tolerability and efficacy of organo-osmium complex FY26 and its tissue pharmacokinetics in hepatocarcinoma-bearing mice.Metallomics : integrated biometal science · 2021Article
- A circadian clock regulates efflux by the blood-brain barrier in mice and human cells.Nature communications · 2021Article
- A mathematical model of the circadian clock and drug pharmacology to optimize irinotecan administration timing in colorectal cancer.Computational and structural biotechnology journal · 2021Article
- Influence of the Circadian Timing System on Tacrolimus Pharmacokinetics and Pharmacodynamics After Kidney Transplantation.Frontiers in pharmacology · 2021Article
- Timing in drug absorption and disposition: The past, present, and future of chronopharmacokinetics.British journal of pharmacology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
P-glycoprotein (P-gp) largely influences the pharmacokinetics (PK) and toxicities of xenobiotics in a patient-specific manner so that personalized drug scheduling may lead to significant patient's benefit. This systems pharmacology study investigated P-gp activity in mice according to organ, sex, feeding status, and circadian time. Sex-specific circadian changes were found in P-gp ileum mRNA and protein levels, circadian amplitudes being larger in females as compared to males. Plasma, ileum and liver concentrations of talinolol, a pure P-gp substrate, significantly differed according to sex, feeding and circadian timing. A physiologically-based PK model was designed to recapitulate these datasets. Estimated mesors (rhythm-adjusted mean) of ileum and hepatic P-gp activity were higher in males as compared to females. Circadian amplitudes were consistently higher in females and circadian maxima varied by up to 10 h with respect to sex. Fasting increased P-gp activity mesor and dampened its rhythm. Ex-vivo bioluminescence recordings of ileum mucosae from transgenic mice revealed endogenous circadian rhythms of P-gp protein expression with a shorter period, larger amplitude, and phase delay in females as compared to males. Importantly, this study provided model structure and parameter estimates to refine PK models of any P-gp substrate to account for sex, feeding and circadian rhythms.
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