Prediction of Systemic Exposure of Ketoprofen Tapes by In Vitro Release Test and Pharmacokinetic Model Analysis: Comparison between Brand-name and Generic Formulations

Keisuke Awa, Hiroki Satoh, Satoko Hori, Yasufumi Sawada

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Topical dermatological formulations of non-steroidal anti-inflammatory drugs (NSAIDs) are reported to show their pharmacological effect partially through the systemic circulation, and to induce systemic side effects. However, pharmaceutical equivalence and pharmacokinetic bioequivalence between brand-name and generic products are not required. Therefore, we aimed to predict systemic drug exposure from brand-name and nine generic ketoprofen tapes. In vitro release profiles were examined using the paddle-over-disk method, then analyzed by the W. I. Higuchi equation incorporating an initial burst effect. Pharmacokinetic parameters were estimated from observed release profiles and the reported time-plasma concentration profile of the brand-name product. Plasma concentration profiles of generic products were predicted from the observed release profiles and the pharmacokinetic parameters of the brand-name product. In vitro release profiles differed markedly, and estimated release rates for initial burst effect and at 24 hours ranged from 4.20 to 88.75% and from 45.27 to 95.83%, respectively. The predicted plasma concentration profile of each product reflected its release profile, and estimated Cmax ranged from 61.70 to 290.30 ng/mL (0.46-to 2.15-fold vs. brand-name product). Generic products were classified into three types, i.e., systemic exposure comparable with, higher than and lower than that of brand-name product. Cmax was predicted to increase with enhanced skin permeability for all products, but the increase rates differed among products. These results suggest that safety and efficacy differ between brand-name and generic ketoprofen tapes. Healthcare professionals should carefully monitor systemic side effects, especially when switching from brand-name to generic products for which higher systemic exposure is predicted.

Original languageEnglish
Pages (from-to)135-144
Number of pages10
JournalYakugaku Zasshi
Volume132
Issue number1
DOIs
Publication statusPublished - 2012 Jan 1
Externally publishedYes

Keywords

  • adverse effect
  • generic product
  • in vitro release test
  • ketoprofen tape
  • pharmacokinetic model
  • systemic exposure

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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