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The drug flux represents the slope of the linear regression of the accumulated mass (Q) over time (t) normalized over the permeation area (A), i.e., the surface area of the barrier available for permeation.
Equation 1:
The drug apparent permeability (Papp) is calculated by normalizing the drug flux (j) over the initial concentration of the API in the donor compartment (c0) as:
Equation 2:
Dimensionally, the Papp represents a velocity, and it is normally expressed in cm/sec. The highest is the permeability, the highest is expected to be the bioavailability of the drug after oral administration.
Permm server and database
a computational tool for theoretical assessment of passive permeability of molecules across the lipid bilayer Medicinal chemistry Diffusion Membrane biology
medicinal chemistry
Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of chemistry and pharmacy involved with designing and developing pharmaceutical drugs. Medicinal chemistry involves the identification, synthesis and developme ...
, Drug Permeability is an empirical parameter that indicates how quickly a chemical entity or an active pharmaceutical ingredient crosses a biological membrane
A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates the interior of a cell from the external environment or creates intracellular compartments by serving as a boundary between one part of the ...
or another biological barrier to become bioavailable
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. ...
in the body. Drug permeability, together with drug aqueous solubility
An aqueous solution is a solution in which the solvent is water. It is mostly shown in chemical equations by appending (aq) to the relevant chemical formula. For example, a solution of table salt, or sodium chloride (NaCl), in water would ...
are the two parameters that define the fate of the active ingredient after oral administration and ultimately define its bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. ...
. When drug permeability is empirically measured ''in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and ...
'', it is generally called apparent permeability (Papp) as its absolute value varies according to the method selected for its measurement. Papp is measured ''in vitro'' utilizing cellular based barriers such as the Caco-2
Caco-2 (from ''Cancer coli'', "colon cancer") is an immortalized cell line of human colorectal adenocarcinoma cells. It is primarily used as a model of the intestinal epithelial barrier. In culture, Caco-2 cells spontaneously differentiate into a ...
model or utilizing artificial biomimetic barriers, such as the Parallel Artificial Membrane Permeation Assay (PAMPA
The Pampas (from the qu, pampa, meaning "plain") are fertile South American low grasslands that cover more than and include the Argentine provinces of Buenos Aires, La Pampa, Santa Fe, Entre Ríos, and Córdoba; all of Uruguay; and Brazil ...
) or the PermeaPad. All these methods are built on an acceptor compartment (from 0.2 up to several mL according to the method uses) where the drug solution is placed, a biomimetic barrier and an acceptor compartment, where the drug concentration is quantified over time. By maintaining sink condition, a steady state
In systems theory, a system or a process is in a steady state if the variables (called state variables) which define the behavior of the system or the process are unchanging in time. In continuous time, this means that for those properties ' ...
is reached after a lag time
Lag, or similar, may refer to:
Lag
* Łąg, Poland
* Lag (company), a French guitar maker
* Lag (cue sports), a brief pre-game competition to determine which player will go first
* Latency (engineering), a slower response time in computing, comm ...
(τ, Fig. 1) .
Data Analysis
The drug flux represents the slope of the linear regression of the accumulated mass (Q) over time (t) normalized over the permeation area (A), i.e., the surface area of the barrier available for permeation.
Equation 1:
The drug apparent permeability (Papp) is calculated by normalizing the drug flux (j) over the initial concentration of the API in the donor compartment (c0) as:
Equation 2:
Dimensionally, the Papp represents a velocity, and it is normally expressed in cm/sec. The highest is the permeability, the highest is expected to be the bioavailability of the drug after oral administration.
See also
*Lipinski's rule of five
Lipinski's rule of five, also known as Pfizer's rule of five or simply the rule of five (RO5), is a rule of thumb to evaluate druglikeness or determine if a chemical compound with a certain pharmacological or biological activity has chemical pro ...
*Pharmacodynamics
Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms ( ...
*Pharmacokinetics
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...
References
{{reflistExternal links
Permm server and database
a computational tool for theoretical assessment of passive permeability of molecules across the lipid bilayer Medicinal chemistry Diffusion Membrane biology