Download (how much drug, how often etc.) Bad kinetics

Pharmacokinetics
Mathematic descript. of A) Biolog. processes affecting drugs
B) Biolog. processes affected by drugs drugs
•Mathematical expressions to describe temporal changes in drug conc.
•Determine constrains related to ADME processes
Optimal dossage regime
(how much drug, how often etc.)
Bad kinetics -- Need for improved structure
Compartment models
One compartment modell
C
The whole body = central compartment
Drug rapidly distributed thru out the body
Two compartment model
C
P
Central compartment (plasma etc)
Peripher compartment (certain tissue, organs etc)
Linear Pharmacokinetics
•1. order process; Rate (biotransformation)  Size of Dose
•Drug transported by passive diffusion
•Drug conc in organ  Size of Dose
•t 1/2 elimination, elimination rate const independent of Dose
Biotransformation:
•transformation of drugs between “compartments”
•absorbtion
•elimination
Non-Linear Pharmacokinetics
0. order kinetics
•Rate of biotransformation independent of Dose
•Carrier-Protein with a given max capasity involved in biotransform. (Michaelis-Menten)
More complicated situations:
•Reabsorb. of drug in kidney
•Metabolites inhib. their own formation (neg. feed back)
The appearant volume of distribution (V)
•Normally characteristic of drug (not biolog. systhem)
•Influenced by certain diseases (changes in blood compossition, tot. body fluid, tussue permeability)
•Independent of drug conc. (lineær pharmacokinetics)
Dose
V=
(Cp)0
(Cp)0 = Initial plasma conc.
V: <10 L - >100 L
Clearance (Cl)
•Function of blood flow
•Function of an organs capasity to metabol. / excrete
•Hypothetic vol. of distribution from which the drug is removed / time
Q Conc. arteria = rate into organ
Liver / Kidney
Q Conc. vein = rate out of organ
Metabolism / excretion
Rate elim = Q
(CA - CV)
Extract. ratio (E) =
Q
(CA - CV)
Q CA
E = 0; No extraction (excretion / metabol.)
E < 0.3; Low extract. ratio
E 0.3 - 0.7; Intermed. extract. ratio
E > 0.7; High. extract. ratio
E = 1; Total extraction
ER = Renal extract. ratio (Kidney)
EH = Hepatic extract ratio (Liver)
Clearance (Cl) = Q
E
Bioavailability
Rate and extent to which the drug reach general circulation
Membrane
GI-tract
Blood
Drug
Often
rate limiting
Plasma
conc
(Cp) max
Acidic /
Enzymatic break down
Binding to
biomolecules
t max
Time
Comparison of plasma conc vs time plots
•Different drug
•Same drug, different formulation
•Drug with and witout food etc.