Transdermal Delivery of Narcotic Analgesics: Comparative Metabolism and Permeability of Human Cadaver Skin and Hairless Mouse Skin

Abstract. The present study aims to develop the correlation between in vitro and in vivo skin permeation of lidocaine in its transdermal patch. In order to minimize the run-to-run variability during in vitro skin permeation studies, release normalized cumulative percent (%Ct n ) was calculated. A suitable polynomial mathematical model was used to establish a correlation between time and %Ct n . Percent in vivo absorbed was calculated by using numerical deconvolution (NDC) and non-compartmental analysis (NCA) methods. Pharmacokinetic (PK) parameters such as AUC last and C max were predicted with the established in vitro-in vivo correlation (IVIVC) models. The minimum prediction errors in NDC method for C max were found to be −30.9 and −25.4% for studies I (in vivo study in human volunteers with one batch of Lidoderm patch; internal validation) and II (in vivo study in human volunteers with another batch of Lidoderm patch; external validation), respectively, whereas minimum prediction errors in NCA method were relatively low (3.9 and 0.03% for studies I and II, respectively) compared to those in NDC method. The prediction errors for AUC last were found to be less than 2% for both methods and studies. The established method in this study could be a potential approach for predicting the bioavailability and/or bioequivalence for transdermal drug delivery systems.

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“…Human cadaver skin (HCS) was used as the barrier (18). A 0.64-cm 2 patch containing 3.2 mg of drug was placed on the surface of the HCS.…”

Section: Ex Vivo Skin Permeation Studiesmentioning

confidence: 99%

Lidocaine Transdermal Patch: Pharmacokinetic Modeling and In Vitro–In Vivo Correlation (IVIVC)

et al. 2015

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“…The authors concluded that PLO gel of morphine is unlikely to provide systemic concentrations or relief to cancer-related pain. A different study conducted on human cadaver skin reported similar findings and concluded that morphine is a poor candidate for transdermal drug delivery (86). Even studies in animal models could not obtain drug concentrations in plasma (87).…”

Section: Morphinementioning

confidence: 77%

Organogels in Drug Delivery: A Special Emphasis on Pluronic Lecithin Organogels

et al. 2016

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-Organogels have emerged as an alternative carrier for small and macromolecules via transdermal, oral, rectal and ophthalmic routes. Pluronic lecithin organogels (PLO gels) are lecithin-based organogels widely used in compounding pharmacies as a vehicle for enhancing the transdermal permeability of many therapeutic drugs. However, the scientific and systematic evidence in support of how well PLO gels help in transdermal delivery is scanty. Recently, some clinical studies have reported nearly complete lack of bioavailability of certain topically administered drugs from PLO gels. The present review aims at summarizing gels and organogels, with a focus on the use of PLO gels in transdermal drug delivery. A special emphasis is placed on controversies looming over the use of PLO gels as a delivery platform for drugs via transdermal route.

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“…As species differences in skin permeability have been demonstrated since lipid content and water uptake of the stratum corneum vary, results from animal skin are not necessarily transferable to human skin [32][33][34][35]. Therefore it would be of interest to additionally evaluate the pharmacokinetic properties of certain drugs in human skin/animal chimeras which might differ from results drawn by studies on animal skin on animals.…”

Section: Discussionmentioning

confidence: 99%

The SCID-hu Mouse Model as a Tool in Dermatopharmacology Research: New Options and a Review of the Literature

Kappes¹,

Elsner²

2002

Exog Dermatol

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Xenogeneic transplantation of human skin onto severe combined immunodeficiency (SCID) mice lacking functional B and T cells enables the investigation of the human skin organ in vivo by means of an animal carrier. Research on these grafts has yielded a variety of new insights into skin biology and disease. A promising approach is the applicability of this human cutaneous xenograft model for the purpose of drug screening and testing of new therapies. This article reviews the use of the SCID mouse model in terms of dermatotherapy studies and outlines the potential options of this animal model in dermatopharmacology.

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Transdermal Delivery of Narcotic Analgesics: Comparative Metabolism and Permeability of Human Cadaver Skin and Hairless Mouse Skin

Cited by 71 publications

References 18 publications

Lidocaine Transdermal Patch: Pharmacokinetic Modeling and In Vitro–In Vivo Correlation (IVIVC)

Lidocaine Transdermal Patch: Pharmacokinetic Modeling and In Vitro–In Vivo Correlation (IVIVC)

Organogels in Drug Delivery: A Special Emphasis on Pluronic Lecithin Organogels

The SCID-hu Mouse Model as a Tool in Dermatopharmacology Research: New Options and a Review of the Literature

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