Untitled Quiz

Study Notes

Fundamental Pharmacokinetic Parameters:
- Apparent Volume of Distribution (Vd)
- Elimination rate constant (K)
- Elimination half-life (t_1/2)
- Clearance (Cl)

The one-compartment open model with IV bolus administration is the simplest pharmacokinetic model to study fundamental parameters of a drug.
This model assumes uniform distribution of the drug within a single hypothetical compartment.
Drug in the body (DB), apparent volume of distribution (Vd), and elimination rate constant(k) are key variables in the pharmacokinetic model.

Disposition Processes:
- Processes that tend to lower plasma drug concentration.
- Primarily involve distribution and elimination.
Distribution:
- Reversible transfer of a drug between compartments.
Elimination:
- Irreversible loss of a drug from the body.
- Sub-processes: Biotransformation (metabolism) and Excretion.
Steps in Drug Distribution:
- Permeation of free unbound drug from blood to extracellular fluid (ECF).
- Permeation of drug from ECF into intracellular fluid.

Tissue Permeability of the Drug:
- Physicochemical properties of the drug (molecular size, pKa, partition coefficient).
- Physiological barriers to drug diffusion.
Organ/Tissue Size and Perfusion Rate:
Binding of Drugs to Tissue Components:
- Binding to blood components.
- Binding to extravascular tissue proteins.
Apparent Volume of Distribution (Vd):
- Hypothetical volume in which a drug would be dissolved to have the same concentration as in plasma.
- In a real clinical setting, this may differ as body parts don't always have equal concentrations.
- Often described as a factor proportional to the dosing regimen.

A fundamental pharmacokinetic parameter.
Indicates how a drug distributes throughout the body relative to the drug's concentration in plasma.
Indicates extent of distribution into body fluids and tissues.
Helps determine proper dosing regimens and drug behavior.
Body fluids, in proportion to total body weight.
Plasma, interstitial and intracellular components.

Drug concentration (in a compartment) is usually expressed as mg/L.
Plasma concentration immediately after IV bolus injection before significant elimination.
The volume can be calculated from the following formula: V_d = dose / initial drug concentration

Drugs that preferentially bind to plasma proteins have a Vd smaller than the theoretical value.
Drugs that preferentially bind to extravascular tissues have a Vd greater than the theoretical value.

The main interaction in the blood is with plasma proteins.
The binding of drugs to plasma proteins is reversible.
Albumin is the most abundant plasma protein.
The extent/order of drug binding to proteins. (e.g. Albumin > α1-acid Glycoprotein > Lipoproteins > Globulins)

Tissues comprise 40% of body weight which makes tissue-drug binding important.
Tissue binding will affect the apparent volume of distribution.
- If binding is high, Vd will be larger.
- Conversely, if binding is low, Vd will be lower.
Factors influencing localization:
- Lipophilicity
- Structural features
- Perfusion rate
- pH differences

Physicochemical properties of the drug (lipophilicity, partition coefficient, molecular size, ionization)
Degree of tissue and protein binding
Body composition
Blood flow
Age, pregnancy, and diseases
Importance and clinical applications of Vd.
Calculating the total drug amount in the body.
Estimating appropriate loading doses.
Assessing the feasibility of dialysis in overdose cases.