Because pharmacists are professionals who are knowledgeable about drugs more, it is ought that they should be experts in selecting drug products that can produce an equivalent therapeutic effect and contain 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 the 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
- Bioavailability refers to the rate and extent of absorption of a drug from a dosage form as determined by its concentration-time curve in blood or by its excretion in urine. It is a measure of the fraction (F ) of an administered dose of a drug that reaches the systemic circulation in the unchanged form. Bioavailability of drug injected i.v. is 100%, but is frequently lower after oral ingestion because
- the drug may be incompletely absorbed.
- the absorbed drug may undergo first-pass metabolism in the intestinal wall/liver or be excreted in bile.
- Incomplete bioavailability after s.c. or i.m. injection is less common but may occur due to local binding of the drug.
- Bioavailability Indicates a measurement of the rate and extent (amount) of therapeutic active drug that reaches the general circulation.
- It can be also defined as both the relative amount of drug from an administered dosage form that enters the systemic circulation and the rate at which the drug appears in the bloodstream.
Bioequivalence Requirement
- A requirement imposed by the Food and Drug Administration for in vitro and/or in vivo testing of specified drug products must be satisfied as a condition of marketing.
Importance of Bioavailability Studies
- In the market, 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 approve 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
- Clinical studies that are useful in determining the safety and efficacy of the drug product;
- Bioavailability studies which are useful in defining the drug product in terms of its effect on the pharmacokinetics of the drug
- 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 the generic drug products in the markets do not have these studies it is concluded that most of them are ineffective and not safe.
Importance of Bioavailability in the Bioequivalence
- At present, the quality of clinical trials is becoming increasingly important in the public action sense. Relating to their growing importance, the cost of this kind of research is steadily growing. However, not all companies are able to produce original drugs, and not every consumer can afford them, which is why their quality substitutes are needed – generic. To comply with all standards, it is necessary to conduct a bioequivalence study.
- According to the definition of WHO, two drugs are considered bioequivalent, if they are pharmaceutically equivalent, have the same bioavailability, and when used in the same dose ensure proper efficacy and safety.
- Bioavailability is the proportion of the administered dose of an unchanged medical product that enters the bloodstream (the circulatory system). Bioavailability can be either low or high. When injecting directly into the bloodstream, for example, intravenous injection, bioavailability is defined as 100%. Low bioavailability is most typical for oral dosage forms of water-soluble and slowly absorbed drugs.
- The degree of bioavailability is influenced by such indicators as:
- Age
- Sex
- Physical activity
- Genotype
- Stress
- Various disorders and/or transferred operations of the digestive tract
Absolute Bioavailability
- Absolute bioavailability compares the bioavailability of active pharmaceutical ingredients (APIs) in the circulatory system after administration by an intravenous route with the bioavailability of the same medication when administered intravenously. This is the percentage of APIs absorbed because of non-intravenous administration, compared with the corresponding medication administered intravenously. In short, in the case of absolute bioavailability, intravenous administration will be the standard.
Relative Bioavailability
- The relative bioavailability characterizes the bioavailability of the dosage form (A) of a particular medical product when compared with another dosage form (B) of the same drug and is usually the established standard for cases of non-intravenous administration when the administration is via any other channel. In studies of bioequivalence, depending on the goals, both absolute and relative bioavailability indicators are considered.
- From all the above, it is obvious that it is impossible to carry out pharmacokinetic studies (bioequivalence studies) without adequate knowledge of bioavailability.
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 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.
- Bioequivalence of a 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.
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 the competitor's products.
Chemical Name
Name used by the organic chemist to indicate the chemical structure of the drug.
Drug Product
- The finished dosage form (eg, tablet or capsule) that contains the active drug ingredient, is generally but not necessarily associated with inactive ingredients.
- A Drug Product of Dosage Form is the gross pharmaceutical form containing the active ingredient(s) [drug(s)] and excipients substances necessary in formulating a medicament of the desired dosage, desired volume, and preferred application form, ready for administration.
Drug Product Selection
The process of choosing or selecting the drug product in a specified dosage form.
Equivalence
Relation in terms of bioavailability, therapeutic response, or a set of established standards of one drug product to another.
Generic Name
The established, nonproprietary, or common name of the active drug in a drug product (eg, Paracetamol).
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 for the Panadol brand of Paracetamol might be dispensed by the pharmacist as the Calpol brand of Paracetamol if generic substitution is permitted and desired by the physician.
Pharmaceutical Alternative
- Drug products 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 strengths 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).
- 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.
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 route 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, expiration time, and (within certain limits) labeling.
- Drug products that contain identical amounts of identical active drug ingredients, i.e., the same salt or ester of the same therapeutic moiety, in identical dosage forms, but do not necessarily contain the same inactive ingredients.2
Pharmaceutical Substitution
- The process of dispensing a pharmaceutical alternative for the prescribed drug product. For example, ampicillin suspension is dispensed in place of ampicillin capsules, or tetracycline hydrochloride is dispensed in place of tetracycline phosphate. Pharmaceutical substitution generally requires the physician's approval.
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 conditions of use. For example, ibuprofen is given instead of aspirin.
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 drug 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
- Safe and effective
- Pharmaceutical equivalents
- Bioequivalent
- Adequately labeled
- Manufactured in compliance with current good manufacturing practices.
Therapeutic Substitution
The process of dispensing a therapeutic alternative in place of the prescribed drug product. For example, amoxicillin is dispensed for ampicillin.
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