Rate of drug concentration and effect/Metabolism

Rate of drug concentration and effect/Metabolism

During metabolism of a drug it may be altered to a more active or less active form.

Half life of elimination:
• time taken for the concentration of a drug to fall by 50% (t1/2)
• can vary from seconds to many hours
• rapidly removed drugs have a short half life
• reflects the time courses of drug elimination and accumulation and the choice of dosing interval
• derived by plotting concentrations on graph paper (either actual concentrations on semilog graph paper or logged concentrations on linear graph paper)

Bioavailability:
• proportion of an administrated drug which reaches the circulation after administration
• IV administration is 100% bioavailable
• bioavailability following oral administration depends on a number of factors (eg absorption, first pass effect)

First pass (presystemic) effect:
After gastrointestinal absorption (oral administration)  portal vein to liver before entering general circulation. If drug is metabolised in liver  only a proportion will enter general circulation – called first pass effect. Rectal or sublingual route of administration avoids liver.
Eg nitroglycerin – absorbed well but is metabolised by liver on first pass.

Liver metabolism:
The liver is the major site of drug metabolism – aim to make drugs more polar for renal elimination

Two general types of reactions for metabolism of lipid soluble agents:
1) Phase I – convert lipophilic molecules into polar molecule; most reactions use the P-450 systems; these reactions are the basis of one mechanism of interaction of drugs as the cytochrome P-450 enzymes can be inhibited or induced
2) Phase II – conjugation reactions; combine another molecule (mostly glucuronide) with the drug to make it more polar.