Evaluating Within‐Subject Variability for Narrow Therapeutic Index Drugs

2019 ◽  
Vol 105 (2) ◽  
pp. 411-416 ◽  
Author(s):  
Priya Jayachandran ◽  
Hideaki Okochi ◽  
Lynda A. Frassetto ◽  
Wansu Park ◽  
Lanyan Fang ◽  
...  
Keyword(s):  
Therapeutic Index ◽  
Narrow Therapeutic Index ◽  
Subject Variability ◽  
Narrow Therapeutic Index Drugs ◽  
Within Subject Variability

scholarly journals Assessing Bioequivalence of Antiepileptic Drugs: Are the Current Requirements too Permissive?

2014 ◽  
Vol 17 (2) ◽  
pp. 220 ◽  
Author(s):  
Camila F Rediguieri ◽  
Jorge L Zeredo
Keyword(s):  
Antiepileptic Drugs ◽  
Geometric Mean ◽  
Therapeutic Index ◽  
Maximum Deviation ◽  
Strongly Correlated ◽  
Average Difference ◽  
Narrow Therapeutic Index ◽  
Subject Variability ◽  
Clinically Significant ◽  
Narrow Therapeutic Index Drugs

Purpose: In order to evaluate the permissiveness of current bioequivalence requirements for antiepileptic drugs we investigated how accurate Cmax and AUC0-t of generic antiepileptic drugs approved in Brazil are in comparison to reference products. Methods: Data collected from assessment reports of approved bioequivalence studies archived in the Brazilian regulatory agency in 2007-2012 were: geometric mean ratios and 90% confidence intervals (CI) for Cmax and AUC0-t, intra-subject variability (CV) of Cmax and AUC0-t and number of subjects. Results: The average difference in Cmax and AUC0-t between generic and reference products was 5% and 3%, respectively. Maximum deviation from 1.00 of the CI of Cmax can achieve 15-20% (demonstrated in 27% of studies); for AUC0-t, 25% of studies showed the deviation can be >10%. All studies that used adequate number of subjects for a 90% CI of 0.90-1.11 complied with it for AUC0-t, except one of carbamazepine, but only 33% complied with it for both AUC0-t and Cmax. The CV was strongly correlated to the maximum CI deviation for AUC0-t (CV of approximately 15% corresponding to deviation of 10%). Studies that presented maximum CI deviation ≤ 10 % together with CV ≤ 15% for AUC0-t represented 65% of the total. Weaker correlation was observed for Cmax and no correlation was seen between maximum CI deviation and number of subjects. Conclusions: Modification in legislation for bioequivalence of antiepileptic drugs is suggested, not only with constraint of AUC0-t 90% CI to 0.90-1.11, but also with limitation of the CV to 15%, as to assure similar variance in pharmacokinetics and diminish the risk of critical plasma-level fluctuation when switching between generic and reference formulations. Although most generics presented differences ≤ 10% in AUC0-t compared to their references, some narrow therapeutic index drugs displayed differences that could be clinically significant after product substitution.  This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Nano optical and electrochemical sensors and biosensors for detection of narrow therapeutic index drugs

2021 ◽  
Vol 188 (12) ◽  
Author(s):  
Omid Heydari Shayesteh ◽  
Reza Mahjub ◽  
Akram Ranjbar ◽  
Katayoun Derakhshandeh ◽  
Mahdi Jamshidi
Keyword(s):  
Electrochemical Sensors ◽  
Therapeutic Index ◽  
Narrow Therapeutic Index ◽  
Narrow Therapeutic Index Drugs
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