Time-of-day-dependent drug effects: circadian targets; cancer chronotherapy; chronotoxicity; melatonin; clock genes; shift-work; chronopharmacokinetics; cardiovascular + asthma + BP timing.
Chronopharmacology
Circadian drug target
Mure 2018: about 50 percent of mammalian gene expression is rhythmic, and over half of FDA-approved drugs target rhythmic genes;…
Cancer chronotherapy
Levi 1997-2010: 5-FU, oxaliplatin, irinotecan show 2 to 5x toxicity differences and improved tumor response when delivered at specific…
Chronotoxicity
Halberg circadian-dependent LD50: many drugs show 2x to 10x toxicity-dose ratio across the day; exploited for safer dosing in…
Chronesthesy
Time-of-day variation in drug-target sensitivity; e.g., histamine H1 receptor sensitivity peaks at night, beta-2 adrenergic sensitivity…
Melatonin pharmacology
Endogenous SCN-pineal melatonin entrains circadian phase; exogenous melatonin (0.5-5 mg) shifts phase per phase-response curve; ramelteon…
Clock genes (Period / Cry / Bmal1 / Clock)
Hall-Rosbash-Young Nobel 2017: Per/Tim feedback in Drosophila, mammalian Per1/2/3 and Cry1/2 feedback on Bmal1/Clock heterodimer; about…
Shift-work pharmacology
Shift workers show altered drug pharmacokinetics and increased risk for cardiovascular, metabolic, cancer, and mental illness; modafinil…
Chronopharmacokinetics
Time-of-day variation in absorption, distribution, metabolism, excretion; CYP enzyme rhythms (CYP3A4 peaks evening); hepatic blood flow…
Chronotype-based medication timing
Morning-type and evening-type chronotypes (Horne-Ostberg MEQ) shift optimal dosing windows; influences statin, antihypertensive, and…
Cardiovascular chronotherapy
Acute myocardial infarction peaks 6-noon; aspirin platelet inhibition strongest with bedtime dosing; HOPE trial: bedtime ramipril improved…
Asthma corticosteroid timing
Nocturnal asthma worse 4-AM; afternoon (3-PM) inhaled corticosteroid dosing matches eosinophil and cortisol troughs better than morning…
Blood-pressure chronotherapy
MAPEC and Hygia trials (Hermida 2010-2020): bedtime antihypertensive dosing reduced cardiovascular events vs morning; data later contested…
Cortisol circadian rhythm
Saliva-cortisol peak ~30 min after waking (CAR cortisol-awakening-response) + nadir ~midnight; HPA-axis controlled; modulated by light +…
Chrononutrition + meal timing
Asher-Sassone-Corsi 2015: meal-timing entrains peripheral circadian clocks (liver / adipose) independently of central SCN; time-restricted…
Circadian cancer radiotherapy
Bjarnason 1999 / Levi 2007: tumor and normal-tissue radiosensitivity vary across the circadian cycle; rectal-cancer radiotherapy in…
Melatonin timing + blue-light block
Brainard 2001: blue light (460-480 nm) maximally suppresses pineal melatonin via melanopsin-RGC; evening blue-blocking glasses +…
Shift work + type 2 diabetes
Pan-Schernhammer 2011 Nurses Health Study: rotating-shift-work increased T2D risk 28-44% over 18-yr follow-up; circadian-misalignment +…
Chronotype MEQ (Horne-Ostberg)
Horne-Ostberg 1976 19-item Morningness-Eveningness Questionnaire (MEQ): 5 chronotype categories from extreme-morning (70-86) to…