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Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response

Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response

Circadian rhythms are cyclic changes that are crucial in plasma drug concentrations. Various standard circadian parameters, including core body temperature, heart rate, and other cardiovascular factors, directly impact disease states and the therapeutic response to drug therapy.
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...

Circadian Rhythms and Gene Regulation

Circadian Rhythms and Gene Regulation

The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...

Circadian Rhythms and Gene Regulation

Circadian Rhythms and Gene Regulation

The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...

Chronopharmacokinetics: Time-Dependent Pharmacokinetics

Chronopharmacokinetics: Time-Dependent Pharmacokinetics

Chronopharmacokinetics studies the temporal change in drug absorption and elimination. These changes can be cyclical or non-cyclical. Cyclical changes occur over a regular interval, while non-cyclical changes occur over a longer, irregular period.
Time-dependent pharmacokinetics refers to non-cyclical changes in drug rate processes over a period of time. It can lead to nonlinear pharmacokinetics, where the relationship between drug concentration and time is not proportional. Non-cyclical...

Pharmacodynamic Models: Link Model and Systems Pharmacodynamic Model

Pharmacodynamic Models: Link Model and Systems Pharmacodynamic Model

The link model is a fundamental pharmacokinetic-pharmacodynamic (PK–PD) approach to account for delayed drug responses when the observed effect does not immediately correlate with the drug's plasma concentration peak. This delay is mathematically addressed by introducing an effect compartment concentration, Ce, which is kinetically linked to the plasma concentration, Cp, via a first-order rate constant, ke0. The linkage allows for a more accurate prediction of drug effects over time. A higher...

Drug Concentration Versus Time Correlation

Drug Concentration Versus Time Correlation

The plasma drug concentration-time curve is a crucial tool in pharmacokinetics, representing the drug's concentration in plasma at different time intervals post-administration. This curve illustrates the drug's journey from absorption into the systemic circulation, distribution to body tissues, and eventual elimination through excretion or biotransformation.
Two pivotal parameters are the minimum effective concentration (MEC) and the minimum toxic concentration (MTC). The MEC is the lowest drug...

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Related Experiment Video

Updated: May 12, 2026

In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells

In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells

Published on: September 28, 2017

Molecular clocks in pharmacology.

Erik S Musiek¹, Garret A Fitzgerald

¹Department of Neurology, Washington University School of Medicine, 7401 Byron Pl., Saint Louis, MO 63105, USA.

Handbook of Experimental Pharmacology

|April 23, 2013

Summary

Circadian rhythms influence how the body processes drugs, affecting their effectiveness and side effects. Understanding these biological clocks and clock genes is crucial for optimizing drug therapy.

Area of Science:

Chronobiology
Pharmacology
Molecular Biology

Background:

Circadian rhythms govern numerous physiological processes in mammals, leading to daily variations in drug pharmacokinetics and pharmacodynamics.
Diurnal variations in drug absorption, distribution, metabolism, excretion, and target expression are well-documented.
The molecular underpinnings of circadian rhythms involve clock genes, which regulate gene transcription in most cells and tissues.

Purpose of the Study:

To review the role of circadian clocks in drug pharmacokinetics and pharmacodynamics.
To explore the reciprocal interactions between drugs and circadian clock function.
To provide examples of how molecular clock genes regulate pharmacologic parameters.

Main Methods:

Literature review of circadian biology and pharmacology.

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Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures

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Last Updated: May 12, 2026

In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells

In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells

Published on: September 28, 2017

The Use of Mouse Splenocytes to Assess Pathogen-associated Molecular Pattern Influence on Clock Gene Expression

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Published on: July 24, 2018

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures

Published on: November 11, 2016

Analysis of existing data on diurnal variations in drug response.

Synthesis of current research on clock gene regulation of drug metabolism and efficacy.

Main Results:

Circadian clock genes significantly influence drug absorption, distribution, metabolism, and excretion.
Clock gene activity impacts drug efficacy and toxicity profiles.
Drugs can reciprocally affect the expression and function of circadian clock genes.

Conclusions:

Circadian rhythms are critical determinants of drug pharmacokinetics and pharmacodynamics.
Clock genes represent key regulators of drug response.
Further research into chronopharmacology can lead to optimized therapeutic strategies.