Incompatibility refers to interactions between two or more substances which lead to changes in
chemical, physical, therapeutic properties of the pharmaceutical dosage form.
Therapeutic Incompatibility
Definition: It is the modification of the therapeutic effect of one drug by the prior concomitant
administration of another. It is also called drug interactions .
Divided into two groups:
1. Pharmacokinetics Involve the effect of a drug on another from the point of view
that includes absorption, distribution, metabolism and excretion.
2. 2 . Pharmacodynamics Are related to the pharmacological activity of the inter
acting drugs. E.g.: synergism, antagonism, altered cellular transport, effect on the
receptor site.
Pharmacokinetic Interactions
Altered GIT absorption
Displaced protein binding
Altered metabolism
Altered renal execration
1. Altered GIT Absorption
Altered pH
Altered bacterial flora
Formation of drug chelates or complexes
Drug induced mucosal damage and altered GIT motility
a. Altered pH
non-ionized form of a drug is more lipid soluble and more readily absorbed from
GIT than the ionized form does.
(Therefore, these drugs must be separated by atleast 2hours in the time of administration
of both.)
b. Altered Intestinal Bacterial Flora
E.g.: In 10% 0f patients recieve digoxin:40% or more of the administered dose is metabolized by
the intestinal flora.