Proportionality refers to the relationship between the dose of a drug and its effect on the body. In the context of ascending dose studies, proportionality refers to whether the effect of the drug increases in a predictable and proportional manner as the dose is increased.
Ascending dose studies are a type of clinical trial in which the dose of a drug is progressively increased in a predetermined manner in a group of subjects. The purpose of these studies is to determine the appropriate dose of a drug, as well as to identify any potential side effects and determine the maximum tolerated dose (MTD).
Proportionality is an important consideration in ascending dose studies because it allows researchers to predict the effect of the drug at different doses based on the observed effect at a lower dose. If a drug exhibits proportionality, it means that the effect on the body increases in a predictable manner as the dose is increased. For example, if a drug exhibits proportionality, a doubling of the dose should result in a doubling of the effect.
In drug development, it is essential to determine whether the pharmacokinetic parameters of a new drug candidate, for a given dose range, are linear or nonlinear. While it is impossible to establish a complete PK profile for all doses, prediction of drug exposure in a certain dose range can be easily made if the compound possesses the property of dose proportionality(DP). This property is also called dose independent and is related to linear PK.
There are several factors that can influence the proportionality of a drug, including the pharmacokinetic and pharmacodynamic properties of the drug, as well as the characteristics of the subjects being studied (e.g., age, weight, etc.). It is important for researchers to carefully consider these factors when designing and interpreting the results of an ascending dose study.
In the analysis of dose proportionality, by administering different doses of drugs, testing the plasma drug concentration of the compound in the animal body, and calculating the drug exposure, the relationship between the administered dose of the small molecule drug and the body exposure can be calculated.
In the area of in Vivo DMPK, AxisPharm Bioanalysis services offer single ascending dose study and multiple ascending dose study services in species such as mouse, rat, dog, monkey, cat, rabbit, guinea pig, and etc.