Penetration through the Skin Barrier.

The skin is a strong and flexible organ with barrier properties essential for maintaining homeostasis and thereby human life. Characterizing this barrier is the ability to prevent some chemicals from crossing the barrier while allowing others, including medicinal products, to pass at varying rates. During recent decades, the latter has received increased attention as a route for intentionally delivering drugs to patients.

Artefactual skin lesions in children and adolescents: review of the literature and two cases of factitious purpura.

Background: Self harm is a great diagnostic and treatment challenge. In addition, psychocutaneous conditions are rare in the pediatric population and may therefore be misdiagnosed. Dermatitis artefacta is a psychocutaneous syndrome, which is a subgroup of the general spectrum of self-inflicted skin lesions.

Current challenges in bioequivalence, quality, and novel assessment technologies for topical products.

This paper summarises the proceedings of a recent workshop which brought together pharmaceutical scientists and dermatologists from academia, industry and regulatory agencies to discuss current regulatory issues and industry practices for establishing therapeutic bioequivalence (BE) of dermatologic topical products. The methods currently available for assessment of BE were reviewed as well as alternatives and the advantages and disadvantages of each method were considered. Guidance on quality and performance of topical products was reviewed and a framework to categorise existing and alternative methods for evaluation of BE was discussed.

Percutaneous penetration--methodological considerations.

Studies on percutaneous penetration are needed to assess the hazards after unintended occupational skin exposures to industrial products as well as the efficacy after intended consumer exposure to topically applied medicinal or cosmetic products. During recent decades, a number of methods have been developed to replace methods involving experimental animals. The results obtained from these methods are decided not only by the chemical or product tested, but to a significant degree also by the experimental set-up and decisions made by the investigator during the planning phase.

In vitro and in vivo evaluation of three metronidazole topical products.

Two 1% and one 0.75% metronidazole cream products were approved as bioequivalent products. These products were evaluated for their in vivo cutaneous penetration characteristics by dermatopharmacokinetic (DPK) and dermal microdialysis (DMD) sampling methodologies.

Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling.

Background: Methodologies for continuous sampling of lipophilic drugs and high-molecular solutes in the dermis are currently lacking. We investigated the feasibility of sampling a lipophilic topical drug and the locally released biomarker in the dermis of non-lesional and lesional skin of psoriatic patients over 25h by means of membrane-free dermal open-flow microperfusion probes (dOFM) and novel wearable multi-channel pumps.

Methods: Nine psoriatic patients received a topical p-38 inhibitor (BCT194, 0.

Impact of adult atopic dermatitis on topical drug penetration: assessment by cutaneous microdialysis and tape stripping.

Appropriate methodologies for the determination of drug penetration in diseased skin have not yet been established. The aim of this study was to determine the cutaneous penetration of a metronidazole cream formulation in atopic dermatitis, employing dermal microdialysis and tape strip sampling techniques. Non-invasive measuring methods were used for the quantification of the severity of the dermatitis.

Basic drug information given by physicians is deficient, and patients' knowledge low.

Objectives: Our aim was to assess basic drug information given by physicians when prescribing new topical medication and to compare this with outpatients' subsequent knowledge.

Methods: Basic drug information was noted during consultations. Subsequently, patients answered a questionnaire regarding diagnosis, treatment, and satisfaction with the consultation.

Application of dermal microdialysis for the evaluation of bioequivalence of a ketoprofen topical gel.

The purpose was to investigate dermal microdialysis (DMD) for the assessment of the bioavailability of a ketoprofen topical gel formulation and to evaluate this technique as a tool for the determination of bioequivalence. Four microdialysis probes were inserted into the dermis on the volar aspect of the forearms of 18 human subjects and the probes were perfused with normal saline for 60 min. A ketoprofen (2.

A prospective study of patient adherence to topical treatments: 95% of patients underdose.

Background: Adherence is essential to a positive treatment outcome. Whether adequate doses of topically applied drugs are used among patients with dermatologic conditions has not been investigated adequately.

Objectives: The objective of this prospective study was to determine to what extent first-time outpatients with dermatologic conditions apply the appropriate dosage of initial treatment with topically administered medication.

The effect of irritant dermatitis on cutaneous bioavailability of a metronidazole formulation, investigated by microdialysis and dermatopharmacokinetic method.

Background: Determination of drug penetration in diseased skin represents a challenge.

Objective: To compare dermal microdialysis and tape-strip sampling of drug penetration in normal skin and skin with irritant dermatitis.

Methods: The two methodologies were employed simultaneously in 16 healthy volunteers.

One in 3 prescriptions are never redeemed: primary nonadherence in an outpatient clinic.

Background: Despite being essential to medication adherence, redemption of initial prescriptions (ie, primary adherence) has been investigated only sparsely.

Objectives: The objectives were to determine the frequency and risk factors for primary nonadherence among outpatients with dermatologic conditions.

Methods: Every 15th day during 2006, all patients receiving a prescription for an initial treatment with a previously untried medication were studied.

AAPS-FDA workshop white paper: microdialysis principles, application and regulatory perspectives.

Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment.

Bioequivalence of topical formulations in humans: evaluation by dermal microdialysis sampling and the dermatopharmacokinetic method.

The aim of this study was to evaluate the relationship between dermal microdialysis (DMD) sampling and the dermatopharmacokinetic method when employed simultaneously for bioequivalence (BE) investigations of topical formulations. Topical lidocaine cream and ointment (both 5%) was investigated in eight healthy human volunteers (four male, four female). On one forearm, four microdialysis probes in two penetration areas sampled for 5 hours, and on the other arm, tape stripping was performed 30 and 120 minutes after product application.

Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis.

Objective: To determine whether probiotic lactobacilli may alleviate small intestinal inflammation and strengthen the intestinal barrier function in children with atopic dermatitis.

Study Design: In a double-blinded, placebo-controlled, cross-over study, probiotic lactobacilli (Lactobacillus rhamnosus 19070-2 and L reuteri DSM 12246) were administered for 6 weeks to 41 children with moderate and severe atopic dermatitis. Gastrointestinal symptoms were registered before and during treatment and small intestinal permeability was measured by the lactulose-mannitol test.

Breastfeeding and risk of atopic dermatitis, by parental history of allergy, during the first 18 months of life.

The role of breastfeeding in allergic diseases remains controversial. The authors studied the association between breastfeeding and development of atopic dermatitis during the first 18 months of life among children with and without a parental history of allergy. A cohort study of 15,430 mother-child pairs enrolled in The Danish National Birth Cohort was carried out between 1998 and 2000.

Use of an intraluminal guide wire in linear microdialysis probes: effect on recovery?

Background/purpose: For microdialysis studies in the skin, laboratory-made linear probes are often used. Probes can be assembled with or without a stainless-steel guide wire in the lumen of the dialysis fibre. From a theoretical viewpoint, this will alter the performance of the probe.

Differentiated in vivo skin penetration of salicylic compounds in hairless rats measured by cutaneous microdialysis.

The purpose was to investigate the in vivo skin penetration of four 14C-salicylic compounds using microdialysis and to relate dermal concentrations to structural features. Furthermore, to compare two in vivo retrodialysis recovery methods for estimation of true unbound extracellular concentrations. Microdialysis probes were inserted in the dermis of hairless rats.

Atopic dermatitis in young children: diagnostic criteria for use in epidemiological studies based on telephone interviews.

The aim of the study was to establish diagnostic criteria for atopic dermatitis in 1.5-year-old children that could be employed in epidemiological studies of atopic dermatitis based on telephone interviews. In a Danish cohort of 100,000 pregnant women, 4 computer-assisted telephone interviews were carried out.

A comparative study on the skin penetration of pure tryptanthrin and tryptanthrin in Isatis tinctoria extract by dermal microdialysis coupled with isotope dilution ESI-LC-MS.

The indolo[2,1- b]quinazoline alkaloid tryptanthrin has recently been identified as a pharmacologically active compound in Isatis tinctoria, with potent dual inhibitory activity on prostaglandin and leukotriene synthesis. To investigate the skin penetration of tryptanthrin from solutions of pure compound and Isatis extracts, we developed and validated a cutaneous microdialysis model using ex vivo pig foreleg. Microdialysis was performed by placing linear probes in the dermis of the skin in situ, and tryptanthrin concentrations in the dialysates were determined by isotope dilution electrospray ionization LC-MS in the selected ion mode.

Effect of probiotic Lactobacillus strains in children with atopic dermatitis.

Background: Recent studies suggest that oral bacteriotherapy with probiotics might be useful in the management of atopic dermatitis (AD).

Objective: The purpose of this investigation was to evaluate the clinical and anti-inflammatory effect of probiotic supplementation in children with AD.

Methods: In a double-blind, placebo-controlled, crossover study, 2 probiotic Lactobacillus strains (lyophilized Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 122460) were given in combination for 6 weeks to 1- to 13-year-old children with AD.