(3B) Non-Linear Pharmacokinetics

Definition:

• T₅₀ =

• time for concentration to drop by half

🚨 BUT:

• ❌ NOT half-life

• ❌ NOT constant

T₅₀

Key idea:

• T₅₀ changes depending on concentration

T₅₀

Example:

• Time from:

  • 20 → 10 mg/L ≠ time from 100 → 50 mg/L

T₅₀

purpose?

• System may switch:

  • unsaturated → saturated

• will look like pseudo 1st order

SATURATION CONCEPT (AGAIN FOR EMPHASIS)

He keeps repeating:

👉 Always ask:

• Is concentration above Km? → saturated

• Is concentration below Km? → unsaturated

APPLICATION → ALCOHOL (ETHANOL)

KEY CONCEPT:

• Alcohol metabolism is SATURATED at normal doses

🚨 HUGE POINT:

• Even 1 drink → saturation

What we use to model alcohol (ethanol) elimination?

• Michaelis-Menten Kinetics

BLOOD ALCOHOL CONCENTRATION (BAC)

a. Legal limit:

b. You feel effects at:

c. Lethal:

a. Legal limit:

• 0.08% = 0.08 g / 100 mL

b. You feel effects at:

• 0.02%- 0,3%

c. Lethal:

• ~0.5%

JUST READ:

you should be able to convert:

• 0.08% = 0.08 g / 100 mL

• 0.08 g = 80 mg / 100 mL

STANDARD DRINK CONCEPT

Defined as…

SAME alcohol amount:

STANDARD DRINK CONCEPT

Big drink = weaker alcohol (lower %)
Small drink = stronger alcohol (higher %)

 Even if diluted → still same alcohol dose

Alcohol density =

0.798 g/mL

SPECIFIC GRAVITY (IMPORTANT)

• Alcohol density = 0.798 g/mL

👉 Used to convert:

• volume → grams

ABSORPTION OF ALCOHOL

Type:

• First-order absorption

 ABSORPTION OF ALCOHOL

Influenced by:

1. What it’s mixed with

• Water → fastest (high Cmax)

• Sugar/fat → slower (low Cmax)

2. Concentration

• Higher % → faster absorption

3. Food

• Empty stomach → faster

• Full stomach → slower

What 2 concepts we talk about in distribution - overview

• rho

• BAC

DISTRIBUTION

Special symbol:

• ρ (rho) = volume of distribution (Vd)

What affects distribution:

• Sex:

  • Male → higher Vd

  • Female → higher BAC

• Hydration

• Body fat

• Body water

WIDMARK EQUATION (CORE CONCEPT)

Idea:

• Predict max BAC (BLOOD ALCOHOL CONCENTRATION)

 WIDMARK EQUATION

Concept:

• Assume:

  • All alcohol taken at once

👉 Gives:

• THEORETICAL Cmax

WIDMARK EQUATION

Reality:

• Actual curve rises gradually

But:

• Eventually reaches that max line

What 2 concepts we talk about in elimination

• Km

• Vmax

• Widmark Eqaution

ELIMINATION OF ALCOHOL

Key concept:

• Km is VERY LOW

👉 Meaning:

• Almost always:

  • Concentration > Km → saturated

ELIMINATION OF ALCOHOL

Vmax (VERY IMPORTANT):

• Called

•  β (beta) for alcohol

Beta = elimination rate

Typical:

• 0.02 % / hour

ZERO-ORDER ELIMINATION

Equation:

• Concentration = initial − (β × time)

• 👉 Straight line decrease

 FACTORS AFFECTING Alcohol PK

Absorption:

• Dose

• Food

• Beverage type

Distribution:

• Hydration

• Blood flow

Elimination:

• Liver function

• Genetics

• Alcohol use history

• Sex

 EXAM TIP (VERY IMPORTANT)

🚨 He explicitly says:

• If BAC = 5% →

• If BAC too tiny →

👉 Use common sense:

• Normal range:

  • 0.02–0.3%

🚨 He explicitly says:

• If BAC = 5% → WRONG

• If BAC too tiny → also wrong

👉 Use common sense:

• Normal range:

  • 0.02–0.3%