Page 137 - Interactive Theoritical Notes of Bioharmaceutics and pharamcokinetics.docx compressed

PharmD clinical pharmacy program Level 3, Semester 2 Biopharmaceutics & Pharmacokinetics (PT608(

2. Disease States Affecting Distribution

❑ In liver, heart, and renal failure,

 The cardiac output and/or perfusion of blood to various tissues are altered.
❑ A decrease in perfusion to the tissues results in:

 lower rate of distribution and, therefore,
 lower drug concentration in the affected tissues relative to the

plasma drug concentration.

❑ When the tissue that receives poor perfusion is the primary eliminating
organ,

 a lower rate of drug elimination results,
 which then may cause drug accumulation in the body

3. Physico-chemical Properties and lipid Solubility of the Drug

1. Drugs having M. Wt. of ˂ 500 to 600 Daltons easily cross the capillary membrane

to penetrate into the extracellular fluids (except in CNS) because junctions

between the capillary endothelial cells are not tight.

2. Water-soluble molecules and ions of size below 50 daltons enter the cell

through aqueous filled channels, whereas, those of larger size are restricted

unless a specialized transport system exists for them.

3. A drug that is highly lipid soluble easily penetrates most membrane barriers,

which are mainly lipid based, and distributes extensively to fat tissues.

4. Lipid soluble drugs also more readily cross special barriers such as the blood

brain barrier as well as the placental barrier.

5. Drugs that are very polar and therefore hydrophilic (e.g., aminoglycosides) do

not distribute well into fat tissues.

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