TAILIEUCHUNG - Chapter 005. Principles of Clinical Pharmacology (Part 2)

Principles of Pharmacokinetics The processes of absorption, distribution, metabolism, and excretion— collectively termed drug disposition—determine the concentration of drug delivered to target effector molecules. Absorption Bioavailability When a drug is administered orally, subcutaneously, intramuscularly, rectally, sublingually, or directly into desired sites of action, the amount of drug actually entering the systemic circulation may be less than with the intravenous route (Fig. 5-2A ). The fraction of drug available to the systemic circulation by other routes is termed bioavailability. Bioavailability may be . | Chapter 005. Principles of Clinical Pharmacology Part 2 Principles of Pharmacokinetics The processes of absorption distribution metabolism and excretion collectively termed drug disposition determine the concentration of drug delivered to target effector molecules. Absorption Bioavailability When a drug is administered orally subcutaneously intramuscularly rectally sublingually or directly into desired sites of action the amount of drug actually entering the systemic circulation may be less than with the intravenous route Fig. 5-2A . The fraction of drug available to the systemic circulation by other routes is termed bioavailability. Bioavailability may be 100 for two reasons 1 absorption is reduced or 2 the drug undergoes metabolism or elimination prior to entering the systemic circulation. When a drug is administered by a nonintravenous route the peak concentration occurs later and is lower than after the same dose given by rapid intravenous injection reflecting absorption from the site of administration Fig. 52 . The extent of absorption may be reduced because a drug is incompletely released from its dosage form undergoes destruction at its site of administration or has physicochemical properties such as insolubility that prevent complete absorption from its site of administration. Slow absorption is deliberately designed into slow-release or sustained-release drug formulations in order to minimize variation in plasma concentrations during the interval between doses. First-Pass Effect When a drug is administered orally it must transverse the intestinal epithelium the portal venous system and the liver prior to entering the systemic circulation Fig. 5-3 . Once a drug enters the enterocyte it may undergo metabolism be transported into the portal vein or undergo excretion back into the intestinal lumen. Both excretion into the intestinal lumen and metabolism decrease systemic bioavailability. Once a drug passes this enterocyte barrier it may also be taken up into .

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