Free fraction
Free Fraction
The free fraction refers to the portion of a drug or other substance that is not bound to protein in the blood plasma. It is the unbound part of the drug that is pharmacologically active, capable of crossing cell membranes and exerting its effect on the body.
Overview[edit | edit source]
In pharmacokinetics, the free fraction of a drug is a critical determinant of both its distribution within the body and its elimination. Drugs can bind to various proteins in the blood, including albumin, alpha-1-acid glycoprotein, and lipoproteins. The extent of this binding can significantly influence the drug's pharmacokinetics and pharmacodynamics.
Importance in Pharmacokinetics[edit | edit source]
The free fraction of a drug in the blood is the pharmacologically active component. It is this fraction that can diffuse across cell membranes and interact with receptors to produce a pharmacological response. The bound fraction, in contrast, is pharmacologically inactive.
The free fraction is also the fraction that is available for metabolism and excretion. Drugs that are highly bound to plasma proteins may have a longer half-life and a smaller volume of distribution, as they are largely confined to the vascular compartment.
Factors Influencing Free Fraction[edit | edit source]
Several factors can influence the free fraction of a drug. These include the drug's lipophilicity, its pKa, the concentration of binding proteins in the blood, and the presence of other drugs that may compete for binding sites.
Clinical Significance[edit | edit source]
Understanding the free fraction of a drug is important in therapeutic drug monitoring, particularly for drugs with a narrow therapeutic index. Changes in the free fraction can significantly alter the drug's therapeutic effect or toxicity. For example, in patients with hypoalbuminemia, the free fraction of drugs that bind to albumin may be increased, potentially leading to toxicity.
See Also[edit | edit source]
References[edit | edit source]
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