Weeks 3-4

Volume of Distribution

• The volume of distribution (Vd) is the theoretical volume that a drug would occupy if it were distributed evenly throughout the body at the same concentration as in the plasma.
• The units for Vd are liters (L) or milliliters (mL).

Rate of Drug Clearance

• The rate of drug clearance (CL) is the volume of plasma cleared of drug per unit of time.
• The units for clearance are liters per hour (L/hr) or milliliters per minute (mL/min).

Half-life

• The half-life (t1/2) of a drug is the time it takes for the concentration of the drug in the plasma to decrease by half.
• If a child is given a medication with a half-life of 5 hours, they will likely wake up after 10 hours. The medication will have reduced to about 25% of the original dose after 10 hours.
• Half-life is used to determine the dosing frequency of a drug.

Bioavailability

• Bioavailability (F) is the fraction of an administered drug that reaches the systemic circulation unchanged.
• The bioavailability of an oral (po) dose can range from 0% to 100%.

First Pass Effect

• The first-pass effect is the metabolism of a drug in the liver before it reaches the systemic circulation.
• This is illustrated by the example of a 100 mg dose that passes through the liver, and only 95 mg comes out.
• The first-pass effect can be avoided by administering the drug intravenously (IV) or by using a formulation that bypasses the liver.

Maintenance Dose

• The maintenance dose is the dose of a drug that is needed to maintain a therapeutic concentration in the plasma.

Dosing Rate

• The dosing rate is the amount of drug that is administered over a period of time.

Loading Dose

• The loading dose is a larger initial dose of a drug that is given to quickly achieve a therapeutic concentration in the plasma.

Creatinine Clearance

• Creatinine clearance (CC) is a measure of kidney function.
• If a patient's CC is 30 mL/min, their dose should be reduced by 50%.

Drug Elimination

• If a drug is eliminated 50% through the kidney and 50% through the liver, then 250 mg will be eliminated through each organ if the total drug amount is 500 mg.

Biotransformation

• Biotransformation is the process by which a drug is chemically changed in the body.

Phase I of Biotransformation

• Phase I biotransformation involves oxidation, reduction, and hydrolysis reactions.
• CYP enzymes are primarily found in the liver.

Phase II of Drug Metabolism

• Phase II biotransformation involves conjugation reactions, which add a polar group to the drug molecule.
• Phase II biotransformation mostly occurs in the liver.

Induction and Inhibition

• Induction of phase I biotransformation increases the activity of CYP enzymes.
• Inhibition of phase I biotransformation decreases the activity of CYP enzymes.

Example of Induction and Inhibition

• A good example of induction is the increased activity of CYP 3A4 by rifampicin.
• If Drug B is a potent inhibitor of CYP 3A4, Drug A will accumulate in the patient's body and its effects will be enhanced.
• If Drug B is a potent inhibitor of CYP 3A4 and does not rely on CYP 3A4 for its effects, then Drug B levels will remain unchanged in the body.

Test your knowledge on the concept of volume of distribution in pharmacology. This quiz will cover key definitions, calculations, and implications of this important pharmacokinetic parameter. Perfect for students studying medicine or pharmacy.