Metabolism of Propranolol during Percutaneous Absorption in Human Skin

Ademola, John I.; Chow, Carmen A.; Wester, Ronald C.; Maibach, Howard I.

doi:10.1002/jps.2600820802

Cited by 31 publications

(23 citation statements)

References 11 publications

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“…This drawback of homogenate preparations was previously recognized by Choi et al 3 and Ademola et al 25 Differences in both the extent of metabolite formation and in the metabolite patterns were observed in homogenate versus intact skin studies. 26 Moreover, the metabolic activity in intact cell sheets has been found to be higher than that in homogenates. 23 So, cell homogenate data are unsuitable to predict metabolic activities in intact tissues.…”

Section: Discussionmentioning

confidence: 99%

Epidermal Aminopeptidase Activity and Metabolism as Observed in an Organized HaCaT Cell Sheet Model

Steinsträsser¹,

Koopmann²,

Merkle³

1997

Journal of Pharmaceutical Sciences

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Metabolism studies on organized HaCaT keratinocyte cell sheets are reported. Cells were grown on porous membranes to form organized cell sheets of several cell layers, which were considered as a model of viable epidermis. Metabolism was studied by reflection kinetics, with the top side of the cell sheets in contact with a donor solution and the basal side closed by an impermeable backing layer. Metabolite formation was followed by HPLC of substrate and metabolite in the donor. For comparison, studies with homogenized HaCaT cells were also performed. Model substrates were amino acid amides of 4-methoxy-2-naphthylamine (MNA) (i.e., Ala-MNA, Arg-MNA, Glu-MNA, and Leu-MNA). Also Leu-enkephalin was studied as a model peptide. Except for Glu-MNA, all substrates were metabolized in both the organized cell sheet and in the homogenates. In homogenate studies, saturation of the metabolic reaction was reached at <100 nmol mL(-1) substrate, whereas metabolism in organized cell sheets was below saturation (up to 500 nmol mL(-1)) except for Leu-enkephalin that showed saturation at >100 nmol mL(-1). In homogenates, substrate inhibition was found with Leu-MNA (> approximately 20 nmol mL(-1)) but not with Ala-MNA and Arg-MNA, both of which showed saturation. Differences of homogenates versus organized cell sheets are due to the intact organization and enzyme compartmentation of the cell sheets as opposed to the loss of organization and compartmentation in homogenates. Also, diffusion of substrate into cell sheets may be rate limiting.

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Section: Discussionmentioning

confidence: 99%

Epidermal Aminopeptidase Activity and Metabolism as Observed in an Organized HaCaT Cell Sheet Model

Steinsträsser¹,

Koopmann²,

Merkle³

1997

Journal of Pharmaceutical Sciences

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“…In vitro studies of transdermal delivery systems for topical propranolol showed 10.4% to 36.6% skin accumulation of the drug (14). Absorption resulting in systemic bioavailability was 4.1% to 16.1%.…”

Section: Propranololmentioning

confidence: 99%

Topical Treatment of Infantile Hemangiomas – Where Are We Now? / Topikalni tretman infantilnih hemangioma – gde smo danas?

Semkova¹,

Marina²,

Kazandjieva³

2011

Serbian Journal of Dermatology and Venerology

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Infantile hemangiomas are the most common, benign vascular tumors of infancy. Their main feature is spontaneous involution over months to years after an initial phase of rapid proliferation. Small, superficial lesions usually resolve without sequel, but scarring and disfigurement are still possible, while the cosmetic outcome is unpredictable. Thus, inflantile hemangiomas benefit from non-aggressive topical treatment, because it is safe and with an overall outcome comparable to spontaneous involution. The available topical agents reported in the literature to satisfy these requirements are topical beta-blockers, imiquimod and topical corticosteroids. However, none of these have been assessed in randomized controlled trials, and standardized treatment recommendations about precise dosing and patient selection are not available yet.

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“…Prior research has shown systemic absorption of topical b-blockers to be minimal to nonexistent, thus affording them an excellent safety profile associated with limited side effects. 56,57 Current evidence for topical bblocker treatment of IHs includes a host of small retrospective, observational, prospective cohort studies (level IV-V evidence), 2 RCTs (level II evidence), and a recent meta-analysis (level II evidence). Xu and colleagues 58 showed 90% either good or partial responses and 10% were nonresponders to topical 1% propranolol in their level V review of 28 superficial IHs.…”

Section: Topical/intralesional B-blockersmentioning

confidence: 99%