Pharmacokinetics

The term pharmacokinetics is derived from the ancient Greek words “pharmakon” and “kinetikos”, meaning “drug” and “putting in motion” respectively. It is one of the main branches of pharmacology, and refers to the way that the body reacts on and affects a pharmaceutical substance in the body.

From the moment that a drug enters the body, the body recognizes it and processes it in a unique way, according to the individual characteristics of the drug. Pharmacokinetics is the study of how the body reacts to the presence of the drug. This information can be used to improve the administration and use of medicines.

There are four main components of pharmacokinetics: liberation, absorption, distribution, metabolism and excretion (LADME). These are used to explain the various characteristics of different drugs in the body. They are covered in more detail below.

Liberation

Liberation is the process in which a pharmaceutical substance is released from the formulation it is delivered in. This must occur before the drug can be absorbed into the body.

Absorption

Absorption is the process in which a pharmaceutical substance enters the blood circulation in the body. The pharmacokinetic parameters for absorption include:

• Absorption rate constant: absorption rate / amount of drug remaining to be absorbed
• Bioavailability: amount of drug absorbed / drug dose

Distribution

Distribution is the process in which a pharmaceutical substance is dispersed through the fluids and tissues in the body. The pharmacokinetic parameters for distribution include:

• Apparent volume of distribution: amount of drug in body / drug concentration in plasma
• Unbound fraction: unbound drug concentration in plasma / total drug concentration in plasma

Metabolism

Metabolism is the process in which a pharmaceutical substance is transformed into other substances, called metabolites, in the body. The pharmacokinetic parameters for metabolism include:

• Metabolic clearance: drug metabolism rate / drug concentration in plasma

Excretion

Excretion is the process in which a pharmaceutical substance is removed from the body. In rare cases, some drugs may never be completely excreted from the body. They then irreversibly accumulate in the tissues. The pharmacokinetic parameters for excretion include:

• Renal clearance: renal excretion rate / drug concentration in plasma
• Fraction excreted unchanged: renal excretion rate / drug elimination rate

Other pharmacokinetic parameters for all elimination methods (both metabolism and excretion) include:

• Rate of elimination: renal excretion plus extrarenal elimination
• Clearance: rate of drug elimination / plasma drug concentration OR elimination rate constant times the apparent volume of distribution
• Elimination rate constant: drug elimination rate / amount of drug in body OR clearance / volume of distribution
• Biologic half-life for first order elimination drugs: 0.693 / elimination rate constant

Pharmacokinetic Values

There are several mathematical formulas that can be graphically represented to model each of the pharmacokinetic components.

• Acid dissociation constant (pKa)
• Bioavailability
• Solubility
• Absorption capacity

Pharmacokinetic Studies

Research studies in pharmacokinetics are usually carried out in healthy volunteers or patients, to investigate and estimate the interplay between drugs and the body in the general population.

The data obtained from pharmacokinetic studies is very useful, as it provides information for pharmacologists to make decisions about the appropriate design and administration of each drug.

Clinical pharmacokinetics uses this information and applies it in clinical medical practice, to promote the safest and most effective therapeutic use of drugs for each individual patient.

References

• http://www.ncbi.nlm.nih.gov/books/NBK12815/
• http://www.msdmanuals.com/professional/clinical-pharmacology/pharmacokinetics/overview-of-pharmacokinetics
• http://www.ashp.org/doclibrary/bookstore/p2418-chapter1.aspx
• http://www.braingut.com/pharmacokinetics.asp