Overview of pharmaco/toxico kinetics
Bye Elphas Shikokoti Bsc. MLS (MMUST)
.
DRUG/TOXIN PERMEATION
Drugs and toxic substances permeates/move across cellular membrane barriers by three
basic mechanisms
A. Pinocytosis/endocytosis: a process by which the substance e.g is engulfed by
the cell membrane, carried into the cell by pinching off, the formed vesicle and then
released inside the cytosol by
breakdown of the vesicle membrane.
B. Passive diffusion
▪ Involves movement of a drug from a
region of higher concentration to a
region of lower concentration (i.e
along concentration gradient).
▪ It can be aqueous diffusion or lipid
diffusion
-aqueous diffussion occur through
pores
-lipid diffusion through the lipid
bilayer
▪ Moves small non ionized and lipid
soluble, small water-soluble
drug
molecules
C. Carrier mediated transport
▪ a transmembrane protein transports
or pump the drug across the
membrane. These transmembrane protein transport chemicals related to
endogenous molecules
- Levodopa for example is transported by phenylalanine transporter
▪ movement is by active transport or facilitated diffusion
▪ This mode is saturable and can be inhibited
Permeation depends on:
1
, ▪ Solubility- lipid solubility influence movement through lipid bilayers and is
important for most drugs; water solubility can influence permeation through
aqueous phases.
▪ Concentration gradient- drugs diffusion down a concentration gradient-only free
drug forms contribute to the concentration gradient.
▪ Surface area and vascularity- the higher the surface area and vascularity the faster
the movement of drugs.
▪ Barrier thickness
▪ Degree of ionization- only non-ionized form of the drug crosses the cellular
membrane
Pharmacokinetics: what happens to administered drugs over a period, including the
processes of absorption, distribution, localization in tissues,
biotransformation/metabolism and excretion.
2
Bye Elphas Shikokoti Bsc. MLS (MMUST)
.
DRUG/TOXIN PERMEATION
Drugs and toxic substances permeates/move across cellular membrane barriers by three
basic mechanisms
A. Pinocytosis/endocytosis: a process by which the substance e.g is engulfed by
the cell membrane, carried into the cell by pinching off, the formed vesicle and then
released inside the cytosol by
breakdown of the vesicle membrane.
B. Passive diffusion
▪ Involves movement of a drug from a
region of higher concentration to a
region of lower concentration (i.e
along concentration gradient).
▪ It can be aqueous diffusion or lipid
diffusion
-aqueous diffussion occur through
pores
-lipid diffusion through the lipid
bilayer
▪ Moves small non ionized and lipid
soluble, small water-soluble
drug
molecules
C. Carrier mediated transport
▪ a transmembrane protein transports
or pump the drug across the
membrane. These transmembrane protein transport chemicals related to
endogenous molecules
- Levodopa for example is transported by phenylalanine transporter
▪ movement is by active transport or facilitated diffusion
▪ This mode is saturable and can be inhibited
Permeation depends on:
1
, ▪ Solubility- lipid solubility influence movement through lipid bilayers and is
important for most drugs; water solubility can influence permeation through
aqueous phases.
▪ Concentration gradient- drugs diffusion down a concentration gradient-only free
drug forms contribute to the concentration gradient.
▪ Surface area and vascularity- the higher the surface area and vascularity the faster
the movement of drugs.
▪ Barrier thickness
▪ Degree of ionization- only non-ionized form of the drug crosses the cellular
membrane
Pharmacokinetics: what happens to administered drugs over a period, including the
processes of absorption, distribution, localization in tissues,
biotransformation/metabolism and excretion.
2
