CVD WM5 PPharmacokinetics

What is the pH partition hypothesis?

Only unionised (non-polar) drugs cross membranes easily

What form of a drug crosses membranes?

Unionised (non-polar) form

What are the main PK parameters?

Half-life, clearance, volume of distribution, mean residence time (MRT)

What is the formula for half-life?

t₁/₂ = 0.693 / k_elim

What is the relationship between half-life, clearance, and volume of distribution?

t₁/₂ = 0.693 × V / CL

What happens to half-life if clearance increases?

Half-life decreases (shorter)

What happens to half-life if volume of distribution increases?

Half-life increases (longer)

What is the fraction of dose remaining after n half-lives?

(1/2)^n (50% after 1, 25% after 2, etc.)

After 5 half-lives, what percentage of the dose remains?

~3% (3.125%)

What is the formula for clearance from AUC?

CL = Dose / AUC

What is the relationship between AUC and clearance?

Inversely proportional (higher CL = lower AUC)

What is the formula for volume of distribution from AUC?

V = Dose / (k × AUC)

What is Mean Residence Time (MRT)?

Average time a drug molecule stays in the body

What is the relationship between MRT and half-life?

MRT = 1.44 × t₁/₂

What is the one-compartment model?

Body treated as a single well-mixed compartment

What is the two-compartment model?

Body divided into central (plasma) and peripheral (tissues) compartments

What are the two phases of the two-compartment model?

Distribution phase and elimination phase

What is the formula for rate of absorption?

Rate of absorption = k_a × A_a (first-order)

What is the absorption half-life formula?

t₁/₂,a = 0.693 / k_a

What is the difference between zero-order and first-order absorption?

Zero-order = constant rate; first-order = rate proportional to amount remaining

What is the key equation for oral administration?

dA/dt = k_a × A_a - k_elim × A

What is bioavailability (F)?

Fraction of an oral dose that reaches systemic circulation

What is the formula for bioavailability?

F = (AUC_oral / AUC_IV) × (Dose_IV / Dose_oral)

What happens to Cmax if dose is decreased?

Cmax decreases proportionally

What happens to tmax if dose is decreased?

tmax stays the same

What happens to Cmax if absorption is slowed?

Cmax decreases

What happens to tmax if absorption is slowed?

tmax increases (delayed)

What is the method of residuals used for?

Calculating the absorption rate constant (ka)

What is the formula for tmax?

tmax = ln(ka/k) / (ka - k)

When does tmax occur?

When rate of absorption = rate of elimination

What is AUC (Area Under the Curve)?

Total exposure to the drug over time

How is AUC calculated?

Using the trapezoidal rule

What does AUC represent?

Total exposure to the drug

What happens to AUC if clearance increases?

AUC decreases

What is the driving force for drug absorption?

Concentration gradient (Fick's law)

What is the rate-limiting step in absorption?

Usually the dissolution rate or membrane permeability

What is the difference between Cmax and tmax?

Cmax = peak concentration; tmax = time of peak concentration

What is the half-life of absorption?

t₁/₂,a = 0.693 / k_a

What is the relationship between absorption rate constant and half-life?

Higher ka = shorter absorption half-life

What is the distribution phase?

Initial rapid decline in concentration as drug distributes to tissues

What is the elimination phase?

Slower decline in concentration as drug is cleared from the body

What is the terminal phase?

The final log-linear decline in concentration (elimination)

What is the significance of the terminal phase slope?

It gives the elimination rate constant (k_elim)

What is the difference between apparent and true volume of distribution?

Apparent V = Dose / C(0); true V is the actual volume (not directly measured)

What is the effect of protein binding on volume of distribution?

High protein binding = lower V (drug stays in plasma)

What is the effect of tissue binding on volume of distribution?

High tissue binding = higher V (drug leaves plasma)