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.