Study DesignGlossary Term
ICH E4
The study of how the body affects a drug, encompassing the absorption, distribution, metabolism, and excretion of the substance over time.
Pharmacokinetics describes the quantitative relationship between drug dose and concentrations in the body over time, characterizing how organisms process pharmaceutical substances. Often summarized by the acronym ADME, pharmacokinetics encompasses absorption (how the drug enters the systemic circulation), distribution (how the drug disperses throughout body tissues), metabolism (how the drug is chemically modified, primarily in the liver), and excretion (how the drug and its metabolites are eliminated from the body). Understanding these processes is essential for rational dose selection and optimization.
Pharmacokinetic studies generate data on key parameters that inform dosing decisions. The maximum concentration (Cmax) and time to maximum concentration (Tmax) characterize the absorption phase. The area under the concentration-time curve (AUC) reflects total drug exposure. The half-life indicates how long the drug persists in the body and guides dosing frequency. Clearance and volume of distribution describe how efficiently the body eliminates the drug and how extensively it distributes beyond the blood. These parameters, derived from serial blood sampling, provide the quantitative foundation for clinical pharmacology.
Pharmacokinetic considerations influence virtually every aspect of clinical development. Early studies characterize basic PK parameters and assess the impact of food, formulation changes, and route of administration. Population pharmacokinetic analyses identify patient characteristics that affect drug exposure, informing dose adjustments for special populations such as patients with renal or hepatic impairment, elderly individuals, or pediatric patients. Drug-drug interaction studies evaluate whether concomitant medications alter PK, with implications for labeling and clinical use. This pharmacokinetic foundation supports the therapeutic individualization that optimizes treatment outcomes.
Phase I characterization
"The single ascending dose study collected blood samples at 15 timepoints over 72 hours to characterize the pharmacokinetic profile, determining that the drug had a half-life of approximately 12 hours and linear kinetics across the dose range."
Special population study
"Pharmacokinetic analysis in subjects with moderate hepatic impairment revealed a two-fold increase in drug exposure compared to healthy volunteers, leading to a recommendation for dose reduction in patients with liver disease."
The fraction of an administered dose of a drug that reaches the systemic circulation unchanged, and the rate at which this occurs.
A group of participants in a clinical trial who receive a comparator treatment, placebo, or no treatment to serve as a baseline for evaluating the effects of the investigational intervention.
A clinical trial design in which participants receive multiple treatments in sequence, with each participant serving as their own control by receiving all study treatments during different periods.
A systematic approach to increasing the dose of an investigational product during a clinical trial, typically employed in early-phase studies to identify safe and potentially effective dose levels.
A clinical trial in which both the participants and the investigators are unaware of the treatment assignments, providing maximal protection against bias in the conduct and assessment of the study.
ICH E4
The study of how the body affects a drug, encompassing the absorption, distribution, metabolism, and excretion of the substance over time.
Pharmacokinetics describes the quantitative relationship between drug dose and concentrations in the body over time, characterizing how organisms process pharmaceutical substances. Often summarized by the acronym ADME, pharmacokinetics encompasses absorption (how the drug enters the systemic circulation), distribution (how the drug disperses throughout body tissues), metabolism (how the drug is chemically modified, primarily in the liver), and excretion (how the drug and its metabolites are eliminated from the body). Understanding these processes is essential for rational dose selection and optimization.
Pharmacokinetic studies generate data on key parameters that inform dosing decisions. The maximum concentration (Cmax) and time to maximum concentration (Tmax) characterize the absorption phase. The area under the concentration-time curve (AUC) reflects total drug exposure. The half-life indicates how long the drug persists in the body and guides dosing frequency. Clearance and volume of distribution describe how efficiently the body eliminates the drug and how extensively it distributes beyond the blood. These parameters, derived from serial blood sampling, provide the quantitative foundation for clinical pharmacology.
Pharmacokinetic considerations influence virtually every aspect of clinical development. Early studies characterize basic PK parameters and assess the impact of food, formulation changes, and route of administration. Population pharmacokinetic analyses identify patient characteristics that affect drug exposure, informing dose adjustments for special populations such as patients with renal or hepatic impairment, elderly individuals, or pediatric patients. Drug-drug interaction studies evaluate whether concomitant medications alter PK, with implications for labeling and clinical use. This pharmacokinetic foundation supports the therapeutic individualization that optimizes treatment outcomes.
Phase I characterization
"The single ascending dose study collected blood samples at 15 timepoints over 72 hours to characterize the pharmacokinetic profile, determining that the drug had a half-life of approximately 12 hours and linear kinetics across the dose range."
Special population study
"Pharmacokinetic analysis in subjects with moderate hepatic impairment revealed a two-fold increase in drug exposure compared to healthy volunteers, leading to a recommendation for dose reduction in patients with liver disease."
The fraction of an administered dose of a drug that reaches the systemic circulation unchanged, and the rate at which this occurs.
A group of participants in a clinical trial who receive a comparator treatment, placebo, or no treatment to serve as a baseline for evaluating the effects of the investigational intervention.
A clinical trial design in which participants receive multiple treatments in sequence, with each participant serving as their own control by receiving all study treatments during different periods.
A systematic approach to increasing the dose of an investigational product during a clinical trial, typically employed in early-phase studies to identify safe and potentially effective dose levels.
A clinical trial in which both the participants and the investigators are unaware of the treatment assignments, providing maximal protection against bias in the conduct and assessment of the study.