Development of the Dosage Regimen

Define Bioavailability

The amount of drugs in the plasma in its unchanged/biologically active form

What are 3 factors that affect bioavailability

1. First-pass effect

2. Incomplete/unabsorbed drugs

3. Plasma protein binding

What is Vd? (state 2 points)`

1. The apprent volume of distribution

2. A proportionality value used to determine how easily a drug can distribute/achieve a therapeutic level in the bloodstream

What is the formula for Vd?

What does a high Vd value mean compared to a low Vd value?

High Vd: Drug is easily distributed across cells and membranes; the drug has left the blood plasma and has spread into tissue and fat

Low Vd: Drug is harder to distribute across cells and membranes; the drug remains in the blood, meaning the drug has low solubility/permeability

units for Vd

L for adults, L/kg for children

What is a therapeutic concentration range? What are its units and what’s the symbol?

Is the concentration range that the concentration of the drug in the plasma must reach to achieve its therapeutic effect

Units: mg/L, ug/mL Symbol: [D]th

What is the loading dose? What the symbol? What is the formula for it?

1. used to quickly achieve a therapeutic effect on the patient by taking higher doses of the required medication

2. Symbol: Wd

3. Formula: Apparent Volume of Distribution (Vd)  x The Top Value of the Therapeutic Range of the Drug ([D]o)

What to do in terms of calculating the amount required for a single, normal dose of drug

1. Take median of therapeutic range

2. Multiply it by Vd

What to do if bioavailability of drug is less than 100%? How to calculate the amount of drug actually required?

• If patient must be given loading dose: divide it by bioavailability percentage of drug

• If patient must be given a maintenance dose: divide it by bioavailability percentage of drug

Why do we give single/normal maintenance doses after a loading dose? (2)

-Drug must be kept within the therapeutic concentration ranges

• To follow the plateauing principle

• amount of drug exiting body = amount of drugs being out into the body’s system

• We are simply replacing the amount of drug that has been lost

What is half-life? Why do we look at it in the elimination process?

Half-life: The amount of time it takes for the drug’s active system in the body to be reduced by more than half

When will meds reach an equilibrium/plateau stage? When will drugs be considered eliminated from the body?

4 half-lives for when the patient reaches plateau/equilibrium stages: patient actually feels the benefit of the drug

4 half-lives also, to be fully exited the body

What concentration of drug should the patient receive their next dose if they are following repeated dose therapy?

When the concentration of drug in the plasma reaches the lowest value on the range of the therapeutic concentration range.

Formula to determine dosage interval (amount of time elpases before next dose must be given)

[D] = lowest value in therapeutic concentration range

[D]o = highest value in therapeutic concentration range

k = elimination rate constant (0.693)

How do we determine T’s unit?

whatever k’s unit is, T folows suit

What is clearance? What is the formula for clearance?

1. How much plasma is cleared for drugs, per unit/time

What is Maintenance Dose? What is its formula?

• Dose required to have the drug stay in the therapeutic range