What Is A Pharmacokinetic (PK) Study?
Pharmacokinetics (PK) Study: Drug Concentration vs. Time in the Body
A pharmacokinetic study provides the basis for determining drug exposures in the body over time. PK parameters are used in the evaluation of the absorption, distribution, metabolism, and excretion (ADME) processes of drugs.
Absorption, the first topic of PK studies, is the initial process by which drugs enter the blood circulation following dosing. Drug substances in PK lab testing can be administered to the body through several routes such as oral, nasal, dermal, or parenteral. Absorption at the gastrointestinal tract, one of the most common drug absorption sites, is affected by several factors including physicochemical parameters of the drug, gastrointestinal motility, drug concentration, and ionization state at the site of absorption.
Distribution is a reversible drug transfer within the body from one location to another. The distribution of a drug can be influenced by several factors such as lipid-solubility, concentration in plasma and various tissues, and protein binding of drugs in plasma and tissues. PK studies assess whether compounds can distribute throughout the body readily or are confined to the bloodstream once absorbed.
Metabolism, an essential topic of PK analysis, is the process by which a drug is converted to another chemical entity (metabolite). Metabolism happens primarily in the liver and is classified into two broad categories: Oxidative metabolism includes hydrolysis, oxidation, and reduction reactions driven mainly by the cytochrome P450s, monooxygenase systems, and alcohol dehydrogenases. The typical chemical reactions involved in oxidative metabolism include aromatic hydroxylation, aliphatic hydroxylation, oxidative N dealkylation, oxidative O-dealkylation, S-oxidation, reduction, methylation, and hydrolysis. Most often, these reactions increase compound polarity to make a drug more soluble, facilitating elimination through the kidneys. In conjugative metabolism, conjugation occurs by glucuronidation, sulfation, amino acid conjugation, acetylation, or glutathione conjugation to aid elimination. Enzymes involved in conjugation include UDP glucoronyl transferases, aryl sulfatases, N-acetyl transferases, and glutathione S-transferases. Conjugation can serve to inactivate a compound or make it more readily eliminated by urinary or biliary excretion. Several factors influence a drug’s rate of metabolism, including the route of administration, dose, genetics, disease state, and metabolic activity.
Eliminating the drug and other toxic substances from the body, the last topic of the PK study, is known as the process of excretion. Most drugs in the body are eliminated through the urine. Excretion also depends on the solubility of the drug in water. More soluble drugs are excreted faster in the urine. If the excretion is incomplete, the accumulation of compounds in the body can lead to adverse events. Pharmacokinetics study testing should incorporate sufficient sampling times during compound elimination for appropriate assessments of parameters such as elimination half-life and clearance.