Pharmacokinetic Drug-Drug interactions:
The study of the time coarse of absorption, distribution,
metabolism and excretion of drugs and their relationship with the
pharmacological and toxic effects of the drugs is known as pharmacokinetic.
But in pharmacokinetic not only the extent to which the drug
is absorbed, distributed, metabolized or excreted is important but also the
time coarse of these reactions because we say the rate and extent to which the
drug is absorbed, distributed, metabolized or excreted is known as pharmacokinetics
Drug-Drug Interactions.
Not only the extent but also the rate because the rate is as
much important as the extent to which the drug is absorbed.
In pharmacokinetic drug-drug interactions the first
thing is absorption.
Drug-drug interactions in absorption:
Most of the drugs are given by enteral route / oral route.
Administration of drug through oral route the drug has to reach the systemic
circulation and this movement of drug from the site of administration or from
the site of absorption to the systemic circulation in unchanged form is known
as absorption.
The drug is absorbed by various mechanisms
1)
Passive transport
Which
includes?
·
Passive diffusion
·
Faccilated diffusion
2)
Active transport
Majority of the drugs are transported through passive
transport and 90% of the drugs which are given orally are absorbed through
passive diffusion.
In passive diffusion the drug has to cross the lipid bilayer
membrane from the area of higher drug concentration to the area of lower drug
concentration and this movement will continue until an equilibrium is achieved
which is usually not achieved.
According to fick's law of diffusion
dQ/dt = DAK m/w DGIT – DC / h dQ/dt = rate of diffusion
D = diffusion coefficient
A = effective surface area of membrane
K = membrane water partition coefficient h = thickness of
the membrane
DGIT = drug concentration in the GIT
DC = drug concentration in the plasma DGIT – DC =
concentration gradient
M/w = membrane water partition coefficient of the drug So
Actually,
Rate of drug diffusion by passive diffusion depends on
concentration gradient, greater concentration gradient greater will be the rate
of diffusion and in this case in passive diffusion the force of absorption /
diffusion is actually provided by kinetic energy of the drug molecules.
Greater the concentration gradient greater will be the drug
absorption. But if the drug has to pass through lipid bilayer membrane lipid
soluble drug will easily diffuse and which are unionized and small.
Majority of the drugs for example initially given in solid
dosage form, in solid dosage form the drug first has to disintegrate then has
to disaggregate then has to dissolve and after that drug is absorbed.
Rate determining / limiting step:
There are some rate determining / rate limiting steps in
reactions. The slowest step of reaction is known as rate determining step of
reaction.
Gastrointestinal fluid is aqueous in nature, in aqueous
solvents polar substances are easily dissolved but non polar are not easily
dissolved.
Rate determining Step of lipid soluble drugs:
If lipid soluble drug then slowest step in this reaction
from disintegration until absorption is the dissolution so for lipid soluble
drugs the rate determining step is actually the process of dissolution.
Rate determining step of water soluble drugs:
For water soluble drugs the slowest step is actually
absorption. So the rate determining step in case of water soluble drugs is
absorption.
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