Know Common Steps Involved In Clinical Pharmacokinetics Study

Know Common Steps Involved In Clinical Pharmacokinetics Study

To put it simply, pharmacokinetics is the study of what the body does to a drug. Conventionally, four parameters, defined as ADME are used in any PK study. ADME stands for absorption, distribution, metabolism, and excretion as related to a specific drug. These steps may vary on a case-to-case basis, but they do form an important part of clinical pharmacokinetics.

Administration of a Drug and Absorption

Studying pharmacokinetics of a drug generally starts with its administration. An important parameter here is the bioavailability. It represents the percentage (or fraction) of a drug from an administered dosage that enters systemic circulation. Bioavailability is 100% for a drug administered intravenously. It drops for other methods like when a drug is used orally, applied topically, or administered through other methods.

For example, a drug used orally will go through the gastrointestinal tract and have a first-pass metabolism before it enters systemic circulation. A drug administered with this method risks being denatured by gastric acid, sequestered by binding to food, or modified during the first-pass metabolism.

A PK study will generally involve taking regular samples of blood to check for the presence of the drug. Regardless of the route of administration, the test is often performed to check concentrations in blood, plasma, or serum. It is also fruitful to see concentration against time on a graph. The most commonly used graph presents the blood-concentration area under the curve versus time (AUC).

The peak concentrations (Cmax) and the time of peak concentration (Tmax) form useful data points and are gathered. Other data of interest includes half-life time, mean residence time, and volume of distribution at steady state. In clinical pharmacokinetics, this data can form the basis for understanding the absorption ratio, bioavailability, and absorption rate.

Distribution and Efficiency

Once drug molecules enter systemic circulation, the phase can be considered as a distribution. Since regular blood tests will still be in effect during the study, the Cmax, Tmax, and other data points defined above continue to be relevant. Often, the administration of a drug will be immediately followed by absorption and distribution. 

Metabolism and Excretion

Any drug will undergo metabolism and excretion (expulsion from the body). Metabolism will usually see drugs changing from lipid-soluble form to a water-soluble form that is fit for excretion. This change is usually achieved by processes like oxidation, reduction, and hydrolysis. Once the drug is in a water-soluble form, it may be excreted through urine. Depending on the drug and its molecule size, excretion methods may also include feces and expired air.

Evaluation and Analysis

Data gathered throughout the pharmacokinetic process is analyzed for results and efficiency. Well-strategized clinical bioanalysis can be helpful. Any quality analysis method should sustain good laboratory practices as a basis to support further development studies.

A PK study must demonstrate the presence of a drug or its metabolites at an active site. The time and concentration of such presence are also important. Inclusion of toxicity and toxicokinetic data is important to compare with PK data to ensure adverse effects and clinical effects can be managed. 

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