Because
pharmacists are professionals who are knowledgeable about drugs more,
it is ought that they should be expert in selecting of drug products
that can produce equivalent therapeutic effect and containing the
same amount of active drug whenever a substitution or change may
happen. There are terms that are highly needed to familiarize to be
able to facilitate decisions and right therapy for the patient. To
facilitate such decisions, guidelines have been developed by the U.S.
Food and Drug Administration. These guidelines and methods for
determining drug availability are discussed below.
Bioavailability.
Indicates
a measurement of the rate and extent (amount) of therapeutic active
drug that reaches the general circulation.1
It
can be also defined as both the relative amount of drug from an
administered dosage from which enters the systemic circulation and
the rate at which the drug appears in the blood stream.2
Bioequivalence requirement.
A
requirement imposed by the Food and Drug Administration for in vitro
and/or in vivo testing specified drug products which must be
satisfied as a condition of marketing.1,2
Bioequivalent drug products.
Bioequivalent
drug products are pharmaceutical equivalents that have similar
bioavailability (ie, are not significantly different with respect to
rate and extent of absorption) when given in the same more dose and
studied under similar experimental conditions. Some drugs may be
considered bioequivalent that are equal in the extent of absorption
but not in the rate of absorption; this is possible if the difference
in the rate of absorption is considered clinically insignificant, is
not essential for the attainment of effective body drug
concentrations on chronic use, and is reflected in the proposed
labeling. For example, aspirin and acetaminophen are well-absorbed
drugs, and small differences in the rate of absorption are of very
little clinical consequence.1
Bioequivalence
of drug product is achieved if its extent and rate of absorption are
not statistically significantly different from those of the standard
when administered at the same molar dose.2
Brand name.
Trade
name of the drug. This name is privately owned by the manufacturer or
distributor and is used to distinguish the specific drug product from
competitors' products1 (eg, Tempra, Biogesic).
Chemical name.
Name
used by the organic chemist to indicate the chemical structure of the
drug (eg, N-acetyl-p-aminophenol).1
Chemical
equivalents are pharmaceutical equivalents.
Drug product.
The
finished dosage form (eg, tablet or capsule) that contains the active
drug ingredient, generally but not necessarily in association with
inactive ingredients.1
A
Drug Product of Dosage Form is the gross pharmaceutical form
containing the active ingredient(s) [drug(s)] and vehicle substances
necessary in formulating a medicament of desired dosage, desired
volume and desired application form, ready for administration.2
Drug product selection.
The
process of choosing or selecting the drug product in a specified
dosage form.1
Equivalence.
Relation
in terms of bioavailability, therapeutic response, or a set of
established standards of one drug product to another.1
Generic name.
The
established, nonproprietory or common name of the active drug in a
drug product1 (eg, Mefenamic Acid).
Generic substitution.
The
process of dispensing a different brand or unbranded drug product in
place of the prescribed drug product. The substituted drug product
contains the same active ingredient or therapeutic moiety as the same
salt or ester in the same dosage form but is made by a different
manufacturer. For example, a prescription of Motrin brand of
ibuprofen might be dispensed by the pharmacist as Rufen brand of
ibuprofen if generic substitution is permitted and desired by the
physician.1
Pharmaceutical alternatives.
Drug
products that contain the same therapeutic moiety but as different
salts, esters, or complexes. For example, tetracycline phosphate or
tetracycline hydrochloride equivalent to 250mg tetracycline base are
considered pharmaceutic alternatives. Different dosage forms and
strength within a product line by a single manufacturer are
pharmaceutic alternatives (eg, an extended-release dosage form and a
standard immediate-release dosage form of the same active
ingredient).1
Drug
products that contain the identical therapeutic moiety, or its
precursor, but not necessarily in the same amount, or dosage form or
as the same salt or ester.1
Pharmaceutical Equivalents.
Drug
products that contain the same active drug ingredient (same salt,
ester, or chemical form) and are identical in strength or
concentration, dosage form, and rout of administration (eg, diazepam,
5mg oral tablets). Pharmaceutical equivalent drug products must meet
the identical standards (strength, quality, purity, and identity),
but may differ in such characteristics as color, flavor, shape,
scoring configuration, packaging, preservatives, expirationg time,
and (within certain limits) labeling.1
Drug
products that contain identical amounts of identical active drug
ingredient, i.e., the same salt or ester of the same therapeutic
moiety, in identical dosage forms, but not necessarily containing the
same inactive ingredients.2
Pharmaceutical substitution.
The
process of dispensing a pharmaceutical alternative for the prescribed
drug product. For example, ampicillin suspension us dispensed in
place of ampicillin capsules, or tetracycline hydrochloride is
dispensed in place of tetracycline phosphate. Pharmaceutical
substitution generally requires the physician's approval.1
Therapeutic alternatives.
Drug
products containing different active ingredients that are indicated
for the same therapeutic or clinical objectives. Active ingredients
in therapeutic alternatives are from the same pharmacologic class and
are expected to have the same therapeutic effect when administered to
patients for such condition of use. For example, ibuprofen is given
instead of aspirin.1
Therapeutic equivalents.
Therapeutic
equivalents are drug products that contain the same therapeutically
active drug that should give the same therapeutic effect and have
equal potential for adverse effects under conditions set forth in the
labels of these drugs products. Therapeutic drug products may differ
in certain characteristics, such as color, scoring, flavor,
configuration, packaging, preservatives, and expiration date.
Therapeutic equivalent drug products must be (1) safe and effective,
(2) pharmaceutical equivalents, (3) bioequivalent, (4) adequately
labeled, and (5) manufactured in compliance with current good
manufacturing practices.1
Therapeutic substitution.
The
process of dispensing a therapeutic alternative in place of the
prescribed drug product. For example, amoxicillin is dispensed for
ampicillin.1
Importance of Bioavailability Studies
In
the Philippines there are a lot of generic drug products that are
being marketed without bioequivalency studies, clinical studies and
bioavailability studies. It is not that FDA granted these drug
products to be marketed and overlooked these important studies, but
actually it is the company's responsibility to perform such tests and
studies extensively. FDA is only to approved what has been shown to
them and perform also its function before approving these drug
products.
Thus
when a drug company is introducing a new branded drug or generic
drug, the drug should have done (1) clinical studies that are useful
in determining the safety and efficacy of the drug product; (2)
bioavailability studies which are useful in defining the drug product
in terms of its effect on the pharmacokinetics of the drug; whereas
(3) bioequivalency studies are useful in comparing the
bioavailability of a drug from various drug products. Once the drug
products are demonstrated to be bioequivalent, then the efficacy of
these drug products is assumed to be similar.
Because
most of generic drug products in the Philippines do not have these
studies it is concluded that most of them are ineffective and not
safe.
1Shargel,
L and Yu, A.B.C. 1994. Applied Biopharmaceutics and
Pharmacokinetics, 2nd ed., Appleton & Lange,
Norwalk, CT, p193-195
2Ritschel,
W.A. 1992. Handbook of
Basic Pharmacokinetics, 4th ed., Drug Intelligence
Publications, Inc, Hamilton, IL, p 2-12
