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The charge of a molecule depends upon the pH of its solution. In an acidic medium, basic drugs are more charged and acidic drugs are less charged. The converse is true in a basic medium. For example, Naproxen is a non-steroidal anti-inflammatory drug that is a weak acid (its pKa value is 5.0). The gastric juice has a pH of 2.0. It is a three ...
The use of these models allows an understanding of the characteristics of a molecule, as well as how a particular drug will behave given information regarding some of its basic characteristics such as its acid dissociation constant (pKa), bioavailability and solubility, absorption capacity and distribution in the organism.
A drug's removal rate will be determined by the proportion of the drug that is removed from circulation by each organ once the drug has been delivered to the organ by the circulating blood supply. [1] This new concept builds on earlier ideas and it depends on a number of distinct factors: The drugs characteristics, including its pKa.
The stomach's acidic pH and the subsequent alkalization in the intestine modifies the degree of ionization of acids and weak bases depending on a substance's pKa. [1] The pKa is the pH at which a substance is present at an equilibrium between ionized and non-ionized molecules. The Henderson–Hasselbalch equation is used to calculate pKa.
pKa values for acetic, chloroacetic, dichloroacetic and trichloroacetic acids. Inductive effects and mesomeric effects affect the pK a values. A simple example is provided by the effect of replacing the hydrogen atoms in acetic acid by the more electronegative chlorine atom.
Physical properties of the drug (hydrophobicity, pKa, solubility) The drug formulation (immediate release, excipients used, manufacturing methods, modified release – delayed release, extended release, sustained release, etc.) Whether the formulation is administered in a fed or fasted state; Gastric emptying rate; Circadian differences
In the context of pharmacokinetics (how the body absorbs, metabolizes, and excretes a drug), the distribution coefficient has a strong influence on ADME properties of the drug. Hence the hydrophobicity of a compound (as measured by its distribution coefficient) is a major determinant of how drug-like it is.
PKA is one of the most widely researched protein kinases, in part because of its uniqueness; out of 540 different protein kinase genes that make up the human kinome, only one other protein kinase, casein kinase 2, is known to exist in a physiological tetrameric complex, meaning it consists of four subunits. [1]