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 Vd & clearance
Deriving t1
    • ∴↑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%
Graph 1

The [  ] of drug declines exponentially with time

If we take the Cp (ln) of this exponential graph we will be able to derive t ½ & Vd

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 1st 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