Kinetics

Kinetics

1. Purpose

   • Taylor Rx against variation
   • ADME quantitativley
   • Concentration with time

2. Concentration time

   • Absorbtion
     • Rapid increase
     • Slower PO
   • Distrubution
     • Peaks at maximum
     • Metabolism begins
   • Elimination
     • Falls exponentialy
     • Drug removed
   • Exposure
     • Area under the curve
     • mg.h/L

3. Absorbtion

   • Movement into circulation
     • Plasma concentration
   • Extravascular drug administration
   • 100% for IV
   • Bioavailability (F)
     • Fraction of dose into systemic circulation
     • F = AUCpo/AUCiv * Doseiv/Dosepo
     • Total - first pass
     • Fraction or percentage

4. Volume of distrubution

   • Delivery of drug to tissues via arterial blood
   • Transfered into tissues
   • V = Drug in body / plasma concentration
   • Determinants
     • Body mass
     • Blood flow
     • Tissue vs plasma binding
     • Physiochemical properties
     • Guess for Rx
   • Loading dose
     • Inital dose to reach Rx rapidly
     • LD = V * target C

5. Elimination

   • Irreversible removal from the body
   • Mechanisms
     • Metabolism
     • Excretion
   • Clearance
     • Eliminaition efficency
     • Volume of plasma cleared per unit time
     • L/h
     • Clearance = Renal + Hepatic + Other
     • Set in a patient in a state
     • Cl = Dose/AUC
     • Maintanance dose
       • Dose to maintain a target
       • Clearance = dose rate
       • MD (g/h) = CL (L/h) * Target conc (mg/L)
       • May be blocked over many hours
       • Approximated for convenience
   • Elimination = clearance * concentration
     • Pressure * hole
     • Speeds up with concentration
   • Changes with concentration

6. Plasma half life

   • Time taken for drug to fall by 1/2
   • Depends on volume and clearance
   • Constant
     • Irrespective of conc
   • Accumulation and elimination
     • Wearing off
     • Time to steady state
   • T = 0.7 V/CL
     • E^2
     • Determines close enough
   • Elimination
     • 50% at 1 half life
     • 94.5% at 4 half lives
       • "All" gone
       • 4* life = Eliminaiton
   • Decay
     • Exponential
     • Degrades towards T0
   • Accumulation
     • Steady state established
       • Concentration rises
       • Elimination rises
       • 90% complete after 4 lives
       • Dosage = eliminaiton
     • Time to maintainance
       • Jumpstart by loading dose
       • Circulates about curve