What parameter determines bioequivalence between generic and prototypical medications?

From the Guidelines

Bioequivalence between generic and prototypical medications is determined by the absence of a significant difference in the availability of the active ingredient at the site of drug action.

Key Parameters

• The maximum serum concentration of the drug
• The time until the maximum concentration is reached
• The area under the curve based on serum concentration as a function of time 1

Rationale

These parameters are used to establish bioequivalence, which is crucial in ensuring that generic medications are as effective and safe as their brand-name counterparts.

• A study published in the Annals of Internal Medicine found that most peer-reviewed evidence supports the effectiveness of generic drugs compared to brand-name medications, with no evidence of superiority of brand-name medication in 9 classes of cardiovascular medications 1.
• The U.S. Food and Drug Administration also evaluates the bioequivalence of generic medications, as seen in the case of bupropion, where several generic versions were found not to be bioequivalent to the brand-name version 1.

Clinical Implications

• The use of bioequivalence parameters helps to alleviate concerns about the clinical equivalence of brand-name and generic medications, such as thyroid hormone and bupropion 1.
• A systematic review of warfarin found no significant difference in international normalized ratio or dosage changes between patients who switched to brand-name or generic warfarin, supporting the bioequivalence of generic medications 1.

From the Research

Bioequivalence Parameters

The parameter that determines bioequivalence between generic and prototypical medications includes:

• Maximum drug concentration (Cmax) to characterize the absorption rate 2
• Area under the plasma drug concentration-time curve (AUC) to characterize the extent of drug absorption 2, 3, 4

Bioequivalence Criteria

For a generic drug to be approved, both Cmax and AUC must vary only within a certain limited range compared with those for the brand name medication, specifically:

• The 90% confidence interval of the pharmacokinetic (PK) ratio should lie between 0.80 and 1.25 4
• The mean PK value of the generic product should actually lie quite close to that of the reference standard 4

Importance of Bioequivalence

Bioequivalence is a crucial parameter in determining the interchangeability of generic and brand name medications, with implications for:

• Patient outcomes 5
• Doctor-patient relationships 5
• Patient legal rights 5
• Pharmaceutical quality and safety and efficacy 6