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 (hydrophobicity, pKa, solubility)
- The drug formulation (immediate release, excipients used, manufacturing methods, modified release – delayed release, extended release, sustained release, etc.)
- Whether the formulation is administered in a fed or fasted state
- Gastric emptying rate
- Circadian differences
- Interactions with other drugs/foods:
- Interactions with other drugs (e.g., antacids, alcohol, nicotine)
- Interactions with other foods (e.g., grapefruit juice, pomello, cranberry juice, brassica vegetables)
- Transporters: Substrate of efflux transporters (e.g. P-glycoprotein)
- Health of the GI tract
- Enzyme induction/inhibition by other drugs/foods:
- Enzyme induction (increased rate of metabolism), e.g., Phenytoin induces CYP1A2, CYP2C9, CYP2C19, and CYP3A4
- 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
- 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 trials, inter-individual variation is a critical measurement used to assess the bioavailability differences from patient to patient in order to ensure predictable dosing.
Read more about this topic: Bioavailability
Famous quotes containing the words factors and/or influencing:
“Girls tend to attribute their failures to factors such as lack of ability, while boys tend to attribute failure to specific factors, including teachers’ attitudes. Moreover, girls avoid situations in which failure is likely, whereas boys approach such situations as a challenge, indicating that failure differentially affects self-esteem.”
—Michael Lewis (late–20th-century)
“Do you believe that the dead can influence the living?... Could you conceive of a superhuman mentality influencing someone from the other side of death?... There is such a one.... Someone, something that reaches out from beyond the grave and fills me with horrible impulses.”
—Garrett Fort (1900–1945)