B–D
bioavailability The amount of a DRUG’S active
ingredient the body absorbs and the length of time
it takes for that ingredient to cause an effect in the
body. A common means of determining bioavail-
ability is to measure the concentrations of the
drug in the BLOODcirculation or in the URINEat
certain time intervals. Doctors know the spectrum
of bioavailability and calculate DOSAGEto obtain
the desired therapeutic concentration of the drug.
For most drugs the spectrum of activity pro-
vides adequate therapeutic levels and tests to
measure the drug’s concentrations are not neces-
sary. NARROW THERAPEUTIC INDEX(NTI) drugs such as
the anticoagulant warfarin, the antiarrhythmic
digoxin, and HORMONE supplements such as
levothyroxine (thyroid hormone) require diligent
assessment and monitoring because the margin
between therapeutic and toxic is very close. The
doctor may also assess the drug’s bioavailability
through observation of clinical changes, such as
an INFECTIONthat improves with antibiotic therapy
or BLOOD PRESSUREthat drops with antihyperten-
sive medications.
For the most part pharmaceutically equivalent
drugs (generic drugs) have consistent bioavailabil-
ity across manufacturers and are interchangeable
from this perspective. The exceptions are NTI
drugs, for which doctors and pharmacists recom-
mend staying with the same brand name of drug
for the duration of treatment. Which brand does
not matter so much as that the brand remains con-
sistent. This is because even minute variations in
the manufacturing process, as is inherent in differ-
ent formulations of the same drug product, affect
the way the body absorbs and metabolizes the drug.
Other factors that influence bioavailability are
interactions with foods, other drugs, and MEDICINAL
HERBS AND BOTANICALS. Health conditions such as
gastrointestinal MALABSORPTION, renal failure, or
LIVER FAILURE, as well as the person’s age and weight,
and metabolic disorders, also affect bioavailability.
See also EFFICACY; GENERIC DRUG; HALF-LIFE; THER-
APEUTIC EQUIVALENCE.bioequivalence A DRUGthat has the same bio-
logical effect in the body as a substance the body
makes naturally (such as a HORMONEsupplement)
or two or more drugs that have the same BIOAVAIL-
ABILITYand EFFICACY. Bioequivalence is a significant
concern with NARROW THERAPEUTIC INDEX (NTI)
drugs, which require precise and consistent dos-
ing, as well as with generic drugs.
A GENERIC DRUG, which is a different chemical
formulation of equivalent active ingredients com-
pared to the innovator (original) drug, is not nec-
essarily bioequivalent to the INNOVATOR DRUG. That
is, the same drug product from different manufac-
turers may contain the same amounts of active
ingredient though not the same inactive ingredi-
ents or different proportions of inactive ingredi-
ents. The extent to which these differences
influence bioavailability (the amount of the active
ingredient that enters the body) varies among
classifications of drugs and is especially crucial
with NTI drugs.
The US Food and Drug Administration (FDA)
establishes and regulates the parameters of bioe-
quivalence. Drugs that are bioequivalent must fall
within a specific range for the amount of time it
takes for each drug to enter and remain in the
BLOODcirculation.
See also DRUG INTERACTION; ORANGEBOOK, THE;
THERAPEUTIC EQUIVALENCE.cytochrome P450 (CYP450) enzymes A group
of about 60 endogenous enzymes (enzymes the153