Mathematic descript. of A) Biolog. processes affecting drugs B) 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 One compartment modell The whole body = central compartment Drug rapidly distributed thru out the body 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 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) V: 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

Bioavailability Rate and extent to which the drug reach general circulation Comparison of plasma conc vs time plots Different drug Same drug, different formulation Drug with and witout food etc.