Pharmacokinetics

Pharmacokinetics

1. Absorption

   • Transfer from site of admin to systemic circulation
   • Increase SA = Increased speed of A
   • Aq vehicle - Rapidly A

2. Elimination

   • Metabolism
     • Phase one
       • Oxidation
         • Hydroxylation
         • Epoxide
         • Dealkylation
         • Deamination
       • Reduction
       • Hydrolysis
     • Phase Two- conjugation
       • Sulphation
       • Glucuronidatiom
       • Amino Acid
       • Acetylation
       • Methylation
     • Phase three
       • Cytochrome P450
     • Kinetics
       • A. -->. A(m). --> Ae(m)     Km.         K(m)
   • Excretion
   • Irreversible removal of drug from the body
   • Clearance
     • Total CL=Hepatic CL + Renal CL+ other CL
     • CL=QxE
       • <90L/hr , (1.5L/min)
       • High E drug
         • CL=Q
       • Low E drug
         • CL=CLint x Fu
     • CL=Dose/AUC
     • CL=KV
       • T1/2=ln2V/CL
     • Independent of plasma conc, dependent on efficiency
       • First order kinetics
         • Rate=Vmax x C / Km + C
     • Vol of plasma/blood completely cleared of drug in a given time.
     • Greater CL -> smaller AUC, shorter t1/2, same V
     • Renal CL= GFR x Fu
       • 125mL/min
   • Rate of E= CLxPlasma conc.
     • Extraction ratio= rate of E/ presenting conc.
       • Extraction Ratio= (Cart - Cven)/ Cart
   • Bioavailable fraction (F)
     • CL=FDose/AUC
       • AUC only changed by absorption not by rate
     • IV: 1
     • Fraction of unchanged drug that reaches systemic circulation
   • Major - liver M, biliary Ex ! Kidney, urinary M&Ex
   • Minor - lung M, breath Ex, breast milk, skin, alimentary tract

3. Distribution

   • Transfer from one compartment to another
   • V (L)
     • Vi, Vss
       • Vss=Vp + Vt x (Fu/Fut)
     • Vol of blood needed to account for the total amount of drug in the body
       • Amount=Volume x Conc
   • One compartment model
     • Instantaneous distribution
     • V is constant
     • K=E rate constant
     • Enter text here
     • 1st order
       • Rate=Rate constant x amount
       • Rate of e= CL x Conc
   • Two compartment model
     • D equilibrium not instantaneous
       • V increases with time until D equilibrium reached
     • AUC=A/a + B/b
   • Central
   • Peripheral
   • CO=6L/min
   • Q= blood flow
     • Lungs = 10ml/min
     • Fat = 0.03ml/min
     • HBF~ 1.5L/min
     • Portal BF ~ 1.2L/min
     • Artery ~0.3L/min
     • Bile flow ~ 0.5mL/min
     • Increased by massage and excercise. A is the rate cntrolling step.
   • Multi compartment

4. Routes

   • Injections
     • Iv
     • Intra Arterial- targets specific organs
     • Spinal - drugs that don't cross the BBB. Not systemic. ABs, analgesics, antineoplastics
     • Intraperitoneal - high vascularity, large SA. Lipophilic absorbed quickly but variable. Some HFPM. Local targettng, A not complete
     • Intramuscular- High vascularity, variability between diff muscles. Deltoid 10.2 mcg/ml , GM 4.3, Vastus Leteralus 9.2
     • Avoid HFPM
     • Subcutaneous- Moderate vascularity, Q increased by heat + massage. Q is the ARL step. Limited fluid for dissolution. Local E activity; low. Mild pH
     • Intradermal - V. poor vascularity, small SA. Variable permeability. Local E activity: low. A increased by heat and hydration

Imágenes y archivos del mapa