4.9 : Tissue-Drug Binding: Localization of Drugs and its Significance

Body tissues, comprising approximately 40% of the body weight, are crucial in drug distribution and localization. These tissues can serve as drug storage sites, competing with plasma binding sites for drug molecules.

Drugs can bind to different tissue components, enhancing their distribution and localization. The factors influencing drug localization in tissues include the drug's lipophilicity, structural characteristics, tissue perfusion rate, and pH differences. These factors determine the extent and specificity of drug accumulation in various tissues.

Among the organs, drugs primarily bind to the liver, followed by the kidneys, lungs, and muscles. This binding is influenced by specific receptors or enzymes that interact with the drugs. Additionally, some drugs exhibit tissue specificity, preferentially binding to specific tissues. For example, acetaminophen (paracetamol) exhibits a high affinity for binding to the liver. In contrast, imipramine binds selectively to the lungs, and chloroquine tends to bind to the skin and eyes.

In the treatment of prostate cancer, estramustine, a nitrogen-mustard-linked estradiol compound, selectively binds to the prostate. This targeted binding allows the drug to concentrate in the prostate tissue while sparing normal cells, minimizing systemic side effects.

It is important to note that drug interactions within tissues can occur. For instance, mexiletine, when administered to lidocaine-treated patients, can displace lidocaine from tissue binding sites. This displacement elevates the levels of lidocaine in the bloodstream but reduces its distribution to the lungs and kidneys. As a result, using lidocaine-loading doses in combination with mexiletine carries the potential risk of increasing side effects associated with lidocaine.

Understanding drug localization in body tissues has significant implications in pharmacology. It helps optimize drug therapy, predict efficacy, and minimize adverse effects. By considering tissue-specific drug binding and interactions, it allows healthcare professionals to make informed decisions regarding drug dosing, administration, and treatment strategies.