Background: Establishing the bioequivalence of topical drug products is a costly and time-consuming process since, with few exceptions, clinical efficacy trials are required. Objective: To develop a surrogate for clinical bioequivalence testing through evaluation of the kinetics of drug absorption in vitro through excised human skin. Methods: The percutaneous absorption of seven approved generic topical drug products was compared with their corresponding reference products during preclinical development using the Franz diffusion cell. Thereafter, following the conduct of bioequivalence trials and regulatory approval of these products in the United States, clinical data became available to which the in vitro data were compared. Results: In six of the seven cases the in vitro test:reference ratio for total absorption was close to one and indicated that the products were equivalent, in agreement with the clinical data. Results from the seventh case, in which the test:reference ratio was only 0.63, indicated that the in vitro model actually had greater sensitivity than the clinical method to detect small differences between products. Conclusion: These data demonstrate the relevance and predictive power of the in vitro human skin model and strongly support its use as a surrogate for in vivo bioequivalence studies.

This content is only available via PDF.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.