Mod 4 Drug Absorption Flashcards
Factors influencing drug absorption:
Routes of administration
Physicochemical factors
Physiologic factors
the rate and extent at which drugs reach the systemic circulation from the site of administration.
ABSORPTION
Drug absorption plays an important role in the ______ (F) determination since it contributes importantly to the time and extent that drug targets exposure to therapeutic drugs in vivo.
bioavailability
For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by the measurements intended to reflect the rate and extent to which active ingredient or active moiety becomes available at the site of action.
N/A
Rate-Limiting Steps in Drug Absorption
- For solid oral, immediate-release drug products, the rate processes include;
- Disintegration of the drug product and subsequent release of the drug
- Dissolution of the drug in an aqueous environment
- Absorption across cell membranes into the systemic circulation.
In the process of drug disintegration, dissolution, and absorption, the __________________ is determined by the slowest step in the sequence.
rate at which drug reaches the circulatory system
the slowest step in a series of kinetic processes
Rate-limiting step
Except for controlled-release products, disintegration of a solid oral drug product is usually
more rapid than drug dissolution and drug absorption.
N/A
For drugs that have very poor aqueous solubility, the rate at which the drug dissolves (dissolution) is often the slowest step and therefore exerts a rate-limiting effect on drug
bioavailability.
For a drug that has a high aqueous solubility, the dissolution rate is rapid, and the rate at
which the drug crosses or permeates cell membranes is the slowest or rate-limiting step.
N/A
Oral drug absorption process occurs mainly in small intestinal regions, which include:
a. passive transcellular diffusion
b. carrier-mediated transport processes,
c. paracellular transport
d. endocytosis
In general, lipophilic compounds are usually absorbed by passive diffusion through the intestinal epithelium. Absorption of a compound is governed by many processes.
N/A
Two fundamental parameters govern drug absorption:
a. Drug solubility
b. Gastrointestinal permeability
Therefore, the oral bioavailability of a drug is largely a function of its solubility characteristics in
gastrointestinal fluids, absorption into the systemic circulation, and metabolic stability.
N/A
Factors Influencing Drug Absorption:
- Routes of administration
- Physicochemical factors
- Physiologic factors
A drug formulation (eg, tablets, capsules, solutions), consisting of the drug along with other ingredients (excipient), are formulated to be given by various routes (eg, oral, buccal, sublingual, rectal, or parenteral, topical, and inhalational).
Routes of administration
Major consideration in the design of a drug product include the therapeutic objective, the
application site, and systemic drug absorption from the application site.
Physicochemical factors
denotes ratio of the concentration of a drug in two immiscible or slightly miscible phases.
Lipid-Water partition coefficient
❖ Regardless of the route of administration, drugs must be in a solution form. Thus, solid forms (eg, tablets) must be able to disintegrate and deaggregate.
❖ Except for drug formulation given by IV route, a drug must cross several semipermeable cell membranes before it reaches the systemic circulation.
❖ Cell membranes are biologic barriers that selectively inhibit passage of drug molecules. The membranes are composed primarily of a bimolecular lipid matrix, which determines membrane permeability characteristics.
❖ Extravascular delivery routes, particularly oral dosing, are important and popular means
of drug administration but is further complicated by variables at the absorption site, including possible drug degradation and significant inter-and intra-patient differences in
the rate and extent of absorption.
N/A
▪ If the drug is intended for systemic activity, the drug should ideally be completely and consistently absorbed from the application site. The systemic absorption of a drug is
dependent on:
a. The physicochemical properties of the drug
b. Nature of the drug product
c. Anatomy and physiology of the drug absorption site
N/A
A _____ derived from the ratio of concentration of an organic compound, frequently
a drug, in water and an organic phase, usually n-octanol.
partition coefficient
The higher the partition coefficient, the more membrane soluble is the substance.
One of the most important factors that determine the tissue distribution of a drug.
NA
The distribution law is exact only for ideal solutions under the following conditions:
a) When the two liquid phases are completely immiscible
b) When the solute neither associates nor dissociates in either phase
c) When the solute concentration is relatively low
d) When the solute is only slightly soluble in either phase.
➢ Lipid solubility of drug is a major factor affecting the extent of drug distribution, particularly to the brain, where the blood-brain barrier restricts the penetration of polar and ionized molecules.
➢ Inconsistently, drugs that are highly hydrophobic are also poorly absorbed, because they are poorly soluble in aqueous fluid and, therefore, cannot get to the surface of cells.
N/A
At a certain pH, the relative concentration of the ionic and molecular moieties of a drug are given by the Henderson-Hasselbalch equations.
pH partition coefficient
