Pharmacokinetics
PK contribute to the label once the drug has been approved. PK analysis are mainly used in phase one studies. It can have an impact on the study design and cause a change in it. For example, it can affect the frequency at which the study drug doses will be administered.
When a drug is administered it goes through 4 phases:
1) Absorption: How the drug gets into the blood. For example, the route of administration of the drug can affect absorption. The concept of absorption is not applicable to a drug that is directly injected into the blood.
2) Distribution: How the drug moves from the blood to other parts of the body.
3) Metabolism: How the drug is broken down or transformed by the body into smaller molecules known as metabolites.
4) Excretion: How the drug is removed from the body.
In order to plot a PK profile, blood samples are taken before and after dosing with IMP. Typically, the samples will be taken at the following timepoints:
- pre-dose,
- post-dose every 30 minutes,
- every hour
- at greater time points
From these sample the following PK parameters will be measured. Here are some examples PK parameters:
- Cmax: the maximum concentration recorded
- tmax: the time take to reach Cmax
- AUC (Area Under the Curve): a measure of the exposure to the drug
- t1/2 (elimination half-life): the time taken for the plasma concentration to fall by half its original value
From these parameters the following elements can be determined:
- Bioavailability: It indicates the proportion of drug absorbed into the blood.
- Dose Proportionality: it determines if there is a constant ratio between the dose given and the PK profile.
- Steady State: If a drug is administered continuously over a period of time, it determines if the process of absorption is happening at exactly the same rate. The time taken to reach steady state depends on the half-life of the drug.
