3.10:
Drug Distribution: Tissue Binding
After entering systemic circulation, drugs can distribute into the interstitial fluid and the intracellular fluid of various tissue cells.
As drugs bind to different cellular components, their accumulation may occur in various tissues.
Drugs bound to tissue components serve as reservoirs that slowly release the free drug, prolonging drug action.
However, drug accumulation may cause local toxicity. For example, acrolein, the metabolic product of cyclophosphamide, binds to renal tissues and accumulates in renal cells, exerting its nephrotoxic effects.
Lipophilic drugs bind to body fat, and since fat is a poorly perfused tissue, it serves as a stable drug reservoir for such drugs.
Bones may also function as drug storage sites. An example is treating osteoporosis using alendronate therapy.
The phosphonate binds to hydroxyapatite crystals in the mineralized bone matrix and resists degradation, preserving the bone matrix.
Bones may also function as a reservoir for toxic metals. The slow release of toxins into the blood can give rise to a range of adverse effects.
3.10:
Drug Distribution: Tissue Binding
Upon entering the systemic circulation, drugs can distribute into the interstitial and intracellular fluid of various tissue cells. This distribution is facilitated by the binding of drugs to different cellular components within tissues, which may lead to drug accumulation in specific areas. Drugs bound to tissue components serve as reservoirs that release free drugs back into the system, prolonging the drug's overall action. However, this accumulation can also result in local toxicity.
For instance, acrolein, a metabolic byproduct of cyclophosphamide, binds to renal tissues and accumulates within renal cells, causing nephrotoxic effects. Lipophilic drugs, on the other hand, tend to bind to body fat. Since fat is a poorly perfused tissue, it functions as a stable drug reservoir for these drugs. Additionally, bones can act as drug storage sites, as seen in the treatment of osteoporosis using alendronate therapy. In this case, the phosphonate binds to hydroxyapatite crystals in the mineralized bone matrix, resisting degradation and preserving the bone structure. Moreover, bones can serve as reservoirs for toxic metals, which may be released slowly into the bloodstream, leading to various adverse effects.