Mathematic descript. of A) Biolog. processes affecting drugsB) Biolog. processes affected by drugs drugs
Pharmacokinetics
•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
C
One compartment modell
The whole body = central compartmentDrug rapidly distributed thru out the body
C P
Two compartment model
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 Pharmacokinetics0. 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)
V =Dose
(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
Liver / Kidney
Metabolism / excretion
Q Conc. arteria = rate into organ Q Conc. vein = rate out of organ
Rate elim = Q (CA - CV) Extract. ratio (E) = Q (CA - CV)
Q CA
E = 0; No extraction (excretion / metabol.)E < 0.3; Low extract. ratioE 0.3 - 0.7; Intermed. extract. ratioE > 0.7; High. extract. ratioE = 1; Total extraction
ER = Renal extract. ratio (Kidney)EH = Hepatic extract ratio (Liver)
Clearance (Cl) = Q E
BioavailabilityRate and extent to which the drug reach general circulation
Drug
GI-tractBlood
Membrane
Acidic / Enzymatic break down
Often rate limiting
Binding to biomolecules
Plasma conc
Timet max
(Cp) max
Comparison of plasma conc vs time plots•Different drug•Same drug, different formulation•Drug with and witout food etc.
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