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Monteiro‐Riviere, Nancy A.; Inman, Alfred O.; Riviere, Jim E.; McNeill, Stephen C.; Francoeur, Michael L.

doi:10.1023/a:1018973814456

Cited by 63 publications

(7 citation statements)

References 8 publications

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“…Anyway, difference in the permeation rates of the three model drugs between YMP and human skin are probably due to differences in skin barrier function among species. 16,26,31) In the present study, the inter-and intra-individual variations in YMP skin permeability were found to be smaller than those in human skin permeability. In addition, the interand intra-regional variations in YMP skin permeability were remarkably smaller than the inter-and intra-individual variations in human skin permeability, and were similar to the inter-individual variations in SD rat skin permeability.…”

Section: Discussioncontrasting

confidence: 59%

“…1,[17][18][19][20][21][22] It has been reported that the histological characteristics and permeability properties of pig skin closely resemble those of human skin. 6,7,[23][24][25][26][27][28] In addition, the Yucatan micropig (YMP) has been utilized for numerous research applications and has been suggested as an animal model for biomedical research because of their physiological and morphological similarity to humans. 29) In addition to its hairless feature, YMP has been reported to be similar clinical, structural, immunohistochemical and reactivity properties to human skin.…”

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confidence: 99%

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Variation Assessment for in Vitro Permeabilities through Yucatan Micropig Skin

Takeuchi

Terasaka

Sakurai

et al. 2011

Biological & Pharmaceutical Bulletin

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Animal skins are frequently used as an alternative to human skin in percutaneous absorption studies, because human skin is not always available and the use of human tissues and organs creates ethical problems. In addition, a large variation has been found among human skin specimens as a result of differences in gender, age, race and anatomical donor site. [1][2][3][4][5][6][7][8][9][10] Numerous animal models, including primate, porcine, mouse, rat, guinea pig and snake, have been utilized for skin permeability studies. 1,3,4,[11][12][13] Animal skins with a small variation in skin permeability may be much better than human skin for determining or estimating the skin permeability of drugs and for developing transdermal formulations. 1,14,15) In our earlier study, 16) we investigated the in vitro permeation studies of the three model drugs, nicorandil (NR), isosorbide dinitrate (ISDN) and flurbiprofen (FP), through human abdominal skin (human skin) and Sprague-Dawley rat dorsal skin (SD rat skin) were performed using Franz-type diffusion cells. The three model drugs were selected because of their different log K ow (logarithm of octanol/water partition coefficient at 37°C) (Table 1). NR, ISDN and FP were used as hydrophilic, lipophilic and highly lipophilic drugs, respectively. The permeation rates of the three model drugs were determined, and their variations were evaluated. The inter-individual variations in human skin permeability for each model drug were larger than the intra-individual variations in human skin permeability. Although the interindividual variations in SD rat skin permeability for each model drug were much lower than those in human skin permeability, and the permeation rates of those drugs through the SD rat skin were approximately twice that through human skin.16) The markedly smaller variation in the permeability through SD rat skin compared with that through human skin indicated that the in vitro permeation studies using SD rat skin would be particularly useful for evaluating differences in the skin permeability of the three model drugs as well as for predicting human skin permeability. Recently, pig skin has been frequently used for skin permeation studies. 1,[17][18][19][20][21][22] It has been reported that the histological characteristics and permeability properties of pig skin closely resemble those of human skin. 6,7,[23][24][25][26][27][28] In addition, the Yucatan micropig (YMP) has been utilized for numerous research applications and has been suggested as an animal The purpose of this study was to evaluate the variations in the in vitro Yucatan micropig (YMP) skin permeabilities of drugs and to clarify whether YMP skin can be used to predict human skin permeability. In vitro permeation studies of the three model drugs, nicorandil, isosorbide dinitrate and flurbiprofen, through YMP skin were performed using Franz-type diffusion cells. The permeation rates of the three model drugs were determined, and their variations were evaluated. The inter-individual variations in YMP skin permeab...

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Section: Discussioncontrasting

confidence: 59%

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confidence: 99%

Variation Assessment for in Vitro Permeabilities through Yucatan Micropig Skin

Takeuchi

Terasaka

Sakurai

et al. 2011

Biological & Pharmaceutical Bulletin

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“…Figure 12 shows an example of his work [95]. An important contribution is their finding that deep tissue penetration may relate to the vascularity below the site of topical application [96]. His group has also explored the predictability of solute penetration from complex vehicles [97] and worked with his wife Nancy on studies assessing the safety of nanomaterials [98,99,100,101,102].…”

Section: My Generation - the Baby Boomersmentioning

confidence: 99%

Solute-Vehicle-Skin Interactions in Percutaneous Absorption: The Principles and the People

Roberts¹

2013

Skin Pharmacol Physiol

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An appreciation of solute-vehicle-skin interactions underpins our current understanding of the processes of percutaneous absorption as well as in the prediction of the extent of absorption. This understanding has been reached through principles developed and validated over the last century through the work of a number of authors, including Dale Wurster, Takeru Higuchi, Irvin Blank, Robert Scheuplein, Gordon Flynn, Boyd Poulsen and Tom Franz, as well as by many scientists from my and younger generations. Their work has led to an appreciation of the rate-limiting steps in percutaneous penetration, the role played by the physicochemical properties of the solute, vehicle and skin and the variability that may arise from using various experimental/mathematical/pharmacokinetic models to quantify absorption as well as enabling the prediction of local and systemic efficacy and toxicity. In addition, unexpected behaviour may result from non-ideality in solute-vehicle-skin effects, including dehydration, chemical enhancement, supersaturation, metabolism, sequestration and vascular effects, including those of nanosystems on the local vasculature. In general, in vitro skin penetration profiles are predictive of in vivo profiles but a number of exceptions also exist.

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“…Most drugs are taken up by these vessels to migrate to the systemic circulation, whereas a portion is further diffused into deeper tissues such as the subcutis and muscle. 1,2) If the applied drug is a prodrug, a peptide or an oligonucleotide that can be readily metabolized in skin, its metabolism makes the skin disposition of the drug very difficult.Such dermato-pharmacokinetics have been analyzed by several in vitro and in vivo studies.3,4) Figure 1 schematically illustrates and compares the in vitro and in vivo skin dispositions of a drug and its metabolite after topical application. Overall skin permeations of the drug and its metabolites can be evaluated from the results of in vitro skin permeation experiments (Fig.…”

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confidence: 99%

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confidence: 99%

Analysis of Skin Disposition and Metabolism of Ethyl Nicotinate after Topical Application Using Dual Agar Gel Disc-Inserted Rats

Hasegawa

Kawazome

Matsumoto

et al. 2008

Biological & Pharmaceutical Bulletin

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Following application of a topical formulation to the skin surface, the drug penetrates the stratum corneum, the uppermost layer of skin, and passes through the viable epidermis and dermis to reach the cutaneous vessels. Most drugs are taken up by these vessels to migrate to the systemic circulation, whereas a portion is further diffused into deeper tissues such as the subcutis and muscle. 1,2) If the applied drug is a prodrug, a peptide or an oligonucleotide that can be readily metabolized in skin, its metabolism makes the skin disposition of the drug very difficult.Such dermato-pharmacokinetics have been analyzed by several in vitro and in vivo studies.3,4) Figure 1 schematically illustrates and compares the in vitro and in vivo skin dispositions of a drug and its metabolite after topical application. Overall skin permeations of the drug and its metabolites can be evaluated from the results of in vitro skin permeation experiments (Fig. 1a). Information on enzyme distribution may be obtained by in vitro experiments using split or sliced layers of excised skin.5) It is difficult, however, to determine the effects of the bloodstream on the drug disposition and metabolism in skin from in vitro methods. In contrast, body fluids and tissues are sampled for in vivo percutaneous absorption experiments (Fig. 1b). It is possible to evaluate each fraction of the drug amount from the formulation to the systemic circulation or deeper skin tissues against the initial amount applied to skin. On the other hand, the time course of changes in the drug level in the skin tissues is not easy to follow due to difficulty in consecutive sampling, although some studies had achieved to give in-depth consideration for using multi-compartment model. 6,7) In addition, the metabolic rate of a prodrug in the systemic circulation and the liver is generally so rapid that the metabolic rate in skin cannot be followed from the systemic pharmacokinetics. When such a prodrug is topically applied with the expectation of therapeutic effects after systemic absorption of its parent drug, the total (prodrugϩparent drug) amount permeated through the The skin disposition and metabolism of topically applied ethyl nicotinate (EN) were evaluated in dual agar gel disc-inserted hairless rats, which have two agar gel discs subcutaneously inserted into the abdominal region as drug receptors, and a topical formulation containing EN placed on either side of the gel disc through the skin. Plasma and agar levels of EN and its metabolite, nicotinic acid (NA), were followed every 2 h over 6 h. EN permeated through the skin barrier and partly metabolized to NA with 89.4% of the metabolite ratio [NA/(EN؉NA)] at 6 h. Some EN and NA in the skin moved to the systemic circulation, and the remainder migrated into the agar gel below the formulation. The total amount (EN؉NA) in the skin that distributed from the formulation directly to the systemic circulation and the application side of the gel corresponded to 95.2% and 4.8% of the total skin permeation at 6 h, respectively...

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Cited by 63 publications

References 8 publications

Variation Assessment for in Vitro Permeabilities through Yucatan Micropig Skin

Variation Assessment for in Vitro Permeabilities through Yucatan Micropig Skin

Solute-Vehicle-Skin Interactions in Percutaneous Absorption: The Principles and the People

Analysis of Skin Disposition and Metabolism of Ethyl Nicotinate after Topical Application Using Dual Agar Gel Disc-Inserted Rats

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