ISSN:0011-9059    

DOI:10.1111/j.1365-4362.1992.tb04003.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractAfter reviewing the history of generic drug substitution policy in the United States, this paper discusses issues of equivalence as they apply to topical drug products. Documentation of bioequivalence of topical products has been problematic, and current methods are being re‐evaluated by the Food and Drug Administration, The FDA is currently evaluating various extensions of the basic methodology of the Stoughton‐McKenzie vasoconstrictor assay, in order to develop a more comprehensive pharmacodynamic methodology for documenting topical drug bioequivalence. A modern pharmacodynamic model is described, based on nonlinear dose‐response relationship, a baseline effect, and a maximum or plateau effect. The Agency's goal is a bio‐equivalent methodology that will be simple, readily performed, and based on more objective methods of measuring the vasoconstrictor r

ISSN:0011-9059    

DOI:10.1111/j.1365-4362.1992.tb04004.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractAnimal models allow for testing the potency of topical corticosteroids by measuring their effects on induced conditions that are analogous to human skin disease. Animal models can examine the anti‐inflammatory, anti‐allergic, antiproliferative, and atrophogenic effects of topical corticosteroids. These test models as they are currently applied are relatively imprecise; however, innovations using newly available histologic, autoradiographic, and biochemical techniques have great potential for precisely quantitating the effects of corticosteroids in animal model syst

ISSN:0011-9059    

DOI:10.1111/j.1365-4362.1992.tb04005.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractIt would be useful to have a safe, reliable, reproducible, and inexpensive human test model to determine the potency of topical corticosteroids and the bioequivalence of generic agents. Existing human test systems include erythema or inflammation induced by irritants or other stimuli, experimentally induced cutaneous disease‐like states, and bioassays in patients with psoriasis. None of these systems is currently reliable enough to warrant general use. Among the shortcomings of existing test systems are the difficulty of producing a uniform, steroid‐responsive test condition, the requirement to use occlusion in several of the systems, and the lack of agreement among the results of different tests. Despite these shortcomings, some of the tests may prove useful in comparing innovator and generic topical corticosteroids and in screening the potency of new age

ISSN:0011-9059    

DOI:10.1111/j.1365-4362.1992.tb04006.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0011-9059    

DOI:10.1111/j.1365-4362.1992.tb03511.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractAn ideal method for measuring the bioavailability of topical corticosteroids should be simple, accurate, and adaptable to a variety of settings and should not require extensive special training to perform. Drug uptake into the stratum corneum, measured by tapestripping, is correlated with the pharmacodynamic response of skin blanching, observed in the vasoconstrictor assay. Differences in stratum corneum drug uptake can be objectively quantitated as a function of time, occlusion, dose applied, and vehicle. Tapestripping measurements are reproducible within individual subjects, but large interindividual variabilities may exist. The chromameter, a new technology, objectively quantitates color numerically and can be used to measure skin blanching as part of the pharmacodynamic response to topical corticosteroids. The chromameter offers an easy, objective method with which to quantitate the pharmacodynamic response of topical corticosteroids. Both methods allow a more mechanistic approach than currently used methods to investigate topical drug pharmacokinetics and pharmacodynamics.

ISSN:0011-9059    

DOI:10.1111/j.1365-4362.1992.tb04007.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0011-9059    

DOI:10.1111/j.1365-4362.1992.tb03512.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractStudies that examine the pharmacokinetics of topical drugs at their site of action in the skin have been difficult to perform and, therefore, limited in number. In the early years of topical drug pharmacokinetic research, investigators had to rely on the measurement of less direct indicators of drug throughput such as blood levels and urinary excretion. Today, advances in theory are impelling pharmacokinetic research in new directions, including the measurement of drug availability in tissue compartments within the skin. This research will lead to greater precision in pharmacokinetic measurement and greater relevance of these measurements to the therapeutic efficacy of topical cortico‐steroids in cutaneous disease state

ISSN:0011-9059    

DOI:10.1111/j.1365-4362.1992.tb04008.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0011-9059    

DOI:10.1111/j.1365-4362.1992.tb03513.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractThe vasoconstrictor assay, when properly performed, is a highly reliable method to determine bioequivalence of generic formulations. Recent research has resolved some of the remaining questions concerning the practical application of the assay. Significant vehicle‐related differences have been observed between the potency of different, supposedly equivalent formulations now on the market. Large differences in concentrations of the active agent in similar vehicles usually have not resulted in corresponding differences in vasoconstrictor assay results. Finally, the time course of drug effects may differ among highly potent and less potent corticosteroids. In general, the higher the potency of the topical corticosteroid, the earlier the maximal effect is observed. This finding suggests that short application of highly potent agents might minimize systemic absorption without sacrificing efficac

ISSN:0011-9059    

DOI:10.1111/j.1365-4362.1992.tb04009.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY