Model analysis of tulobuterol patch formulations to explain the influence of drug release rate and transdermal transfer rate on the plasma concentration profile

Tetsuo Watanabe, Hiroki Satoh, Satoko Hori, Akiko Miki, Hisakazu Ohtani, Yasufumi Sawada

Research output: Contribution to journalArticle

2 Citations (Scopus)


The purpose of this study was to compare the transdermal transfer profiles of brand and generic tulobuterol patch formulations and to evaluate possible changes of in vivo kinetics resulting from increased transdermal transfer by means of pharmacokinetic analysis using reported in vitro drug release rate data and plasma drug concentration profiles. On the assumption that the transdermal transfer rate constant (k2) would be constant (independent of formulation), the drug release rate constant from patch formulation (k1) was predicted to be almost equal to the k2 value (k1≈k2) in the brand formulation, but 2- to 4-fold higher than the k2 value (k1>k2) in the two generic formulations. Under normal conditions, there would be no marked difierence in the plasma concentration profiles among the formulations. However, under conditions where transdermal transfer is increased (that is, higher k2), the plasma tulobuterol concentration was predicted to increase more rapidly, with higher C max, and then to decrease more rapidly in the elimination phase after applying the generic formulations compared with the brand formulation. These difierent behaviors would be seen because the transdermal transfer of the generic formulations would be afiected by k2, whereas k1 is still rate-determining for the brand formulation. These results suggest that bronchial asthma patients with risk factors for impaired skin barrier function, including atopic dermatitis, long-term treatment with steroids, and advanced age, should be carefully monitored for reduced treatment efficacy or adverse drug reactions after application of rapid-release generic tulobuterol patch formulations.

Original languageEnglish
Pages (from-to)1483-1492
Number of pages10
JournalYakugaku Zasshi
Issue number10
Publication statusPublished - 2011
Externally publishedYes



  • Drug release profile
  • Increased transdermal transfer
  • Skin transfer kinetics
  • Time course of the blood concentration
  • Tulobuterol patch formulation

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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