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After entry into the systemic circulation, either by intravascular injection or by absorption from any of the various extracellular sites, the drug is subjected to numerous distribution processes that tend to lower its plasma concentration. Distribution is defined as the reversible transfer of a drug between one compartment to another. Some ...
First-pass metabolism may occur in the liver (for propranolol, lidocaine, clomethiazole, and nitroglycerin) or in the gut (for benzylpenicillin and insulin). [4] The four primary systems that affect the first pass effect of a drug are the enzymes of the gastrointestinal lumen, [5] gastrointestinal wall enzymes, [6] [7] [8] bacterial enzymes [5] and hepatic enzymes.
Multiphasic absorption: Drugs injected intravenously are removed from the plasma through two primary mechanisms: (1) Distribution to body tissues and (2) metabolism + excretion of the drugs. The resulting decrease of the drug's plasma concentration follows a biphasic pattern (see figure). Plasma drug concentration vs time after an IV dose
In the absence of a gut compartment, input can be made directly in the liver. However, in that case local metabolism in the gut may not be correctly described. The case of approximately continuous absorption (e.g. via drinking water) can be modeled by a zero-order absorption rate (here R ing in units of mass over time):
The mechanism of action is a crucial factor in determining effect and toxicity of the drug, taking in consideration the pharmacokinetic (PK) factors. [12] The sort and extent of altered cellular physiology will depend on the combination of the drug's presence (as established by pharmacokinetic (PK) studies) and/or its mechanism and duration of ...
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The field encompasses drug composition and properties, functions, sources, synthesis and drug design, molecular and cellular mechanisms, organ/systems mechanisms, signal transduction/cellular communication, molecular diagnostics, interactions, chemical biology, therapy, and medical applications and antipathogenic capabilities.
For instance, ABC transporters such as Pgp, the MRPs and BCRP limit the absorption of many drugs from the intestine, and pump drugs from the liver cells to the bile [88] as a means of removing foreign substances from the body. A large number of drugs are either transported by ABC transporters themselves or affect the transport of other drugs.