Editing Bioavailability (section)

== Factors influencing bioavailability ==

The absolute bioavailability of a drug, when administered by an extravascular route, is usually less than one (i.e., ''F''< 100%). Various physiological factors reduce the availability of drugs prior to their entry into the systemic circulation. Whether a drug is taken with or without food will also affect absorption, other drugs taken concurrently may alter absorption and first-pass metabolism, intestinal motility alters the dissolution of the drug and may affect the degree of chemical degradation of the drug by intestinal microflora. Disease states affecting liver metabolism or gastrointestinal function will also have an effect.

Other factors may include, but are not limited to:
* Physical properties of the drug ([[Hydrophobe|hydrophobicity]], [[Acid dissociation constant|pKa]], [[solubility]])
* The drug formulation (immediate release, excipients used, manufacturing methods, [[Time release technology|modified release]] – delayed release, extended release, sustained release, etc.)
* Whether the formulation is administered in a fed or [[fasting|fasted]] state
* Gastric emptying rate
* [[Circadian]] differences
* Interactions with other drugs/foods:
** Interactions with other drugs (e.g., [[antacid]]s, alcohol, nicotine)
** Interactions with other foods (e.g., [[grapefruit juice]], [[pomello]], [[cranberry juice]], [[brassica]] vegetables)
* Transporters: Substrate of [[efflux (microbiology)|efflux]] transporters (e.g. [[P-glycoprotein]])
* Health of the [[Human gastrointestinal tract|gastrointestinal tract]]
* [[Enzyme]] induction/inhibition by other drugs/foods:
** Enzyme induction (increased rate of metabolism), e.g., [[Phenytoin]] induces [[CYP1A2]], [[CYP2C9]], [[CYP2C19]], and [[CYP3A4]]
** [[Enzyme inhibitor|Enzyme inhibition]] (decreased rate of metabolism), e.g., grapefruit juice inhibits CYP3A → higher nifedipine concentrations
* Individual variation in metabolic differences
** Age: In general, drugs are metabolized more slowly in fetal, neonatal, and geriatric populations
** [[Phenotype#Phenotypic variation|Phenotypic differences]], [[enterohepatic circulation]], diet, gender
* Disease state
** E.g., [[hepatic]] insufficiency, poor [[renal]] function

Each of these factors may vary from patient to patient (inter-individual variation), and indeed in the same patient over time (intra-individual variation). In [[clinical trial]]s, inter-individual variation is a critical measurement used to assess the bioavailability differences from patient to patient in order to ensure predictable dosing.