J Korean Med Sci.  2009 Feb;24(1):7-12. 10.3346/jkms.2009.24.1.7.

Simulation of the AUC Changes after Generic Substitution in Patients

• Yim DS

• KMID: 1794399
• DOI: http://doi.org/10.3346/jkms.2009.24.1.7

Abstract

To address the debate on the safety of generic substitution quantitatively, the author compared the change in AUC in virtual patients who were simulated for several different scenarios of generic substitution. In four scenarios of original (branded) to generic and generic to generic substitution, 5,000 virtual patients were simulated per scenario using the programming software R. The mean population AUC of generics ranged from 90-110% (scenarios A and B) and 80-123.5% (scenarios C and D) of the AUC of the original. Those patients who had an AUC change (ratio) as a result of drug substitution of less than 0.67 or greater than 1.5 were considered to be in potential danger due to the substitution. We found that less than 6% of patients fell outside of the cutoff range of 0.67-1.5 as a result of original to generic substitution. However, in the case of generic to generic substitution, the proportion was as high as 9-12%. This alerts us to the potential danger of generic substitution, especially for drugs with narrow therapeutic indices.

Keyword

Therapeutic Equivalency; Generic Substitution; Simulation

MeSH Terms

*Area Under Curve
Attitude to Health
Computer Simulation
Drug Prescriptions
Drugs, Generic/*pharmacokinetics/therapeutic use
Humans
Patients/psychology/statistics & numerical data
Software
Therapeutic Equivalency

Figure

• 

  Fig. 1 Simulation results of scenario D, one of the four scenarios. Each histogram represents the AUC ratios of 5,000 virtual patients. The generics in scenario D had a Pop Mean AUC ranging from 80-123.5 (original: 100) and an RV of 10-15% (original: 10%). The proportion of patients falling outside of the ratio margin 0.67-1.5 (shaded zone) was also included. (A) The AUCs fluctuate even when the same patient takes the same original formulation on two occasions because of the RV value, given as 10% in this scenario. (B) AUCGen1_i/AUCOri_i1 in the case of switch from the original to a generic. (C) AUCGen1_i/AUCGen2_i in the case of switch from a generic to another generic.

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