Prediction of drug clearance in humans from laboratory animals based on body surface area

X D Liu1, J Chen

  • 1Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjning, People's of Republic of China. xdliu@jlonline.com

Related Concept Videos

Clearance Models: Noncompartmental Models01:17

Clearance Models: Noncompartmental Models

Clearance is a pharmacokinetic parameter traditionally defined by compartment models, signifying the rate at which a drug is expelled from the body. However, a noncompartmental model offers an alternative method for assessing clearance, primarily employing empirical data obtained after administering a single drug dose.
The noncompartmental approach capitalizes on extensive sampling data, correlating the volume of distribution to systemic exposure and the administered dosage. This method enables...
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance01:07

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion, mediated...
One-Compartment Open Model for IV Bolus Administration: Estimation of Clearance00:56

One-Compartment Open Model for IV Bolus Administration: Estimation of Clearance

Clearance is a key pharmacokinetic parameter that quantifies the volume of body fluid from which a drug is entirely removed within a specific time frame. It is crucial in assessing how a drug is eliminated from the body and has critical clinical applications.
In the one-compartment open model for intravenous (IV) bolus administration, clearance is estimated by dividing the elimination rate by the plasma drug concentration. This equation leverages the elimination rate constant and the apparent...
Clearance Models: Compartment Models01:25

Clearance Models: Compartment Models

Clearance measures drug elimination from the central compartment, including plasma and highly perfused organs like kidneys and liver. Its calculation varies depending on pharmacokinetic models and administration routes. The one-compartment model, for instance, portrays the pharmacokinetics of polar drugs such as aminoglycoside antibiotics administered intravenously and readily excreted in urine. In this case, clearance is influenced by the terminal rate constant (λz) and the total volume of...
Clearance Models: Physiological Models01:09

Clearance Models: Physiological Models

Drug clearance is a critical pharmacokinetic process involving the irreversible removal of drugs from the body through various organs over a specified time period. Physiological models are indispensable in determining organ-specific clearance, defined by the proportion of the drug eliminated per unit of time from the organ's blood volume.
The organ's clearance rate depends on the blood flow to the organ and the extraction ratio (E). The extraction ratio describes the organ's proficiency in drug...
Toxicity Testing in Animals01:23

Toxicity Testing in Animals

Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...