# Biv: Discuss the pharmacokinetic factors that affect drug half life

## Defintion

- The time taken for the [ ] drug to halve

## Deriving t ½

- t ½ depends on
**V**_{d}& clearance

- ∴↑Vd = ↑t ½
- ↑clearance = ↓t ½

- This relationship becomes an equation
- Because t ½ involves halving = inverse of 2 = ln 2
- Ln 2 = 0.693

- By first order kinetics it takes 5 t ½ for a drug to be eliminated 97%

### Vd

**Vd**= the theoretical volume of fluid into which a drug disperses in order to produce an observed plasma [ ]**Affected by:**

## Drug Factors

*Molecular size*

- ↓size = ↑Vd

*Lipid solubility*

- ↑lipophilicity = ↑Vd

*pKa*

- Basic → lower pKa = ↑unionised = ↑Vd
- Acidic → higher pKa = ↑unionied = ↑Vd

* **Charge*

- ↓charge = ↑Vd

* **PPB*

↑PPB = ↓Vd

## Patient Factors

*Blood flow*

- ↑BF = ↑Vd

*Age/TBW*

- TBW ↓age = ↓Vd

∴Vd high in neonates

*Fat*

- ↑fat = ↑Vd lipophilic drugs

*Renal F, hepatic F*

- ↓PPB = ↑Vd

## Clearance

**Clearance**= the amount of plasma cleared of drug per unit time (mL/min)- Only applies 1
^{st}order kinetics

*Clearance (total) = Cl (hepatic) + Cl (renal) + Cl (other)*

### Cl (hepatic)

- Determined HBF & HER
- Low ER → depends on intrinsic clearance & PPB
- High ER → depends on HBF

### Cl (renal)

- Depends on GFR (PPB), reabsorption (passive), secretion (active)

### Cl (other)

- Plasma esterases
- Hoffman elimination
- Lung metabolism