Half Lives

Elimination half life

• time take for drug in plasma conc to fall by 50%

1st Order kinetics

• how most drugs are eliminated

Rate of clearance changes with dose → half life remains constant regardless of drug concentration

• gradient (rate of clearance/elimination) directly proportional concentration

• the higher the concentration the faster the drug is eliminated

• safer → drug removed from system within certain amount of time regardless of conc

• BUT IF extremely high conc → then can shift to zero order as elimination mechanisms SATURATED

Example

10 units of drug → remove ½ conc every units

0 sec → 10 plasma conc

1 sec → 5 plasma conc

2 secs → 2.5 plasma conc

1st order graphs

conc-time graph → exponential decay, but half life constant

rate of clearance - logconc graph → straight line (+ve gradient)

Zero Order

Rate of clearance NEVER change with dose → half life changes with dose

• certain fixed conc of drug removed per unit time

• saturation of hepatic enzymes or secretion of PCT active transporters/pumps saturated

e.g. ½ time btw each half life → 1 molecule removed every second

in 5 sec: 10→5 (1 taken each second)

in 2.5: 5→2.5

in 1.25: 2.5 → 1.25

constant removal interval

zero order graphs

conc-time graph → linear decrease

rate of clearance - conc → flat plateau line (constant clearance)

• gradient = 0

Useful to T1/2 of drug

1. know approximate duration of action → time of removal

2. to estimate appropriate dosing interval

3. good indication to reach steady state of plasma concentration → constant removal → precise points of drug conc in therapeutic window

   • 1st order drug + administer at dosage frequency = to half life → administration at half life intervals

(narrow index → low saftey margin to produce desired effect without undesirable side effects)