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Biomedical subjects

C Surber

Publications and source records attributed to C Surber.

At least 19 recordsLinked to original sources
PubMed1996

Delayed-type hypersensitivity to subcutaneous lidocaine with tolerance to articaine: confirmation by in vivo and in vitro tests.

A 43-year-old woman suffered from recurrent localized swellings and an eczematous dermatitis starting 1 day after an injection of lidocaine. Intradermal patch and lymphocyte transformation tests revealed sensitization to lidocaine and cross-reactivity to the other aminoacylamide local anesthetics bupivacaine, mepivacaine and prilocaine, but not to articane. Contact allergy to the ester local anesthetics benzocaine, procaine and tetracaine, the quinoline or aminoacylamide cinchocaine, and the preservatives methylparaben and metabisulfite, was excluded. A subcutaneous challenge with articaine was well tolerated.

Adult↗
PubMed1995

[Lindane].

In Europe and in the US ectoparasitic diseases are increasingly diagnosed in all classes of society. Modern means of transportation promote the spreading from endemic areas into new regions and therefore questions of therapy are becoming increasingly important. A series of preparations in various galenic formulations and in various concentrations are available to treat the ectoparasitic diseases. Due to reports on Lindane poisonings the clinical use of Lindane preparations for the treatment of scabies and pediculosis has become somewhat controversial. In this article we review older and more recent data on pharmacology, pharmacokinetics and toxicology of gamma-1,2,3,4,5,6-Hexachlorcyclohexan [Lindane]. It is pointed out that in the USA Lindane is offered in 1% preparations whereas in the German speaking Europe only 0.3% preparations are available. This latter concentration is considered as sufficient to treat the ectoparasitosis. Furthermore the use of this remedy and aspects of Lindane resistance are discussed. It is concluded that only through additional in depth education of the patients and their folks successful treatment is possible and intoxication can be prevented.

Dose-Response Relationship, Drug↗
PubMed1995

Delayed hypersensitivity to one low-molecular-weight heparin with tolerance of other low-molecular-weight heparins.

We report a patient who developed infiltrated plaques at the sites of subcutaneous injection of a low-molecular-weight heparin. Skin tests and a lymphocyte transformation test revealed hypersensitivity to sandoparin and heparin sodium. The low-molecular-weight heparins nadroparin and dalteparin were subsequently tolerated without adverse effects. Possible risk factors for sensitization are discussed.

Drug Hypersensitivity↗
PubMed1994

Determination of acitretin in the skin, in the suction blister, and in plasma of human volunteers after multiple oral dosing.

Several HPLC methods for quantification of acitretin and its 13-cis isomer in biological fluids have been described. Only limited data are available on determination of this drug in skin samples. Our objective was to improve the sensitivity and selectivity of existing methods to measure drug in small skin samples from humans treated with acitretin. With a new optimized mobile phase [methanol: acetonitrile (7:3, v/v), purified water with 1.5% (v/v) acetic acid, mixed in a 85:15 ratio (v/v)] and a new internal standard (arotinoid ethyl sulfone), a limit of quantification of 1 ng/g tissue was reached. Nine male volunteers were given an oral daily dose of 50 mg acitretin for up to 28 days. Blood and skin samples (punch and shave biopsies, suction blister skin, and fluid) were taken at various time points during and after treatment. Drug concentration and metabolism in plasma and skin samples appeared to be linked in that the trans-isomer concentration was always higher than the cis-isomer concentration during dosing and 3 h after the last dose. However, 7 and 14 days after the last dose in plasma and in all tissue samples (except the shave biopsy), the all-trans-acitretin concentration rapidly decreased and approached the detection limit. In the shave biopsy, the all-trans-acitretin concentration remained higher than the 13-cis-acitretin concentration. Furthermore, the elimination of two isomers from the shave biopsy was delayed.(ABSTRACT TRUNCATED AT 250 WORDS)

Acitretin↗
PubMed1994

Pastes: what do they contain? How do they work?

BACKGROUND: Pastes are semisolid stiff preparations containing a high proportion of finely powdered material. Powders such as zinc oxide, titanium dioxide, starch, kaolin or talc are incorporated in high concentrations into a preferably lipophilic, greasy vehicle. A clinically distinctive feature which is generally attributed to pastes is the quality to absorb exudates by nature of the powder or other absorptive components. Reviewing the various pharmacopoeias serious doubts arise from the various formulas of pastes and their absorptive features. The zinc oxide pastes of the USP XXII, the DAB 10 and BP 88 (US, German and British pharmacopoeias). are composed of petrolatum, zinc oxide and starch. Petrolatum, a highly lipophilic, water-immiscible vehicle surrounds the powder particles preventing any absorption of water or exudates. OBJECTIVE: The goal of our investigation was to test a simple experimental setting to characterize the clinically important absorptive feature of powders and pastes. METHODS: The absorptive features of the powders were determined by the method of Enslin. The absorptive features of the paste preparations were calculated from the weight difference between the paste preparation before and after incubation with water using a simple standardized procedure. RESULTS: The absorptive features of titanium dioxide, zinc oxide, kaolin, corn starch and methylcellulose powder in pharmacopoeia quality were determined. Zinc oxide and kaolin powder showed the highest absorption of 1,000 mg water/g powder (100%). The water absorption of corn starch and titanium dioxide was 700 and 450 mg/g powder, respectively. The absorptive features of a series of paste preparations were studied in a simple experimental setting. The data show that two-phase pastes consisting of two immiscible components, one (the dispersed or inner phase; powder) being suspended in the other (the continuous or outer phase; lipophilic vehicle), have no absorptive features. In contrast, three-phase pastes consisting of a hydrophilic two-phase emulsion with high concentrations of incorporated powder (cream pastes) show considerable water uptake. CONCLUSIONS: We conclude that the classical two-phase pastes such as the zinc oxide pastes have no absorptive features. On the contrary, these formulations are highly occlusive. Therefore lipophilic pastes are only indicated when protection of intact skin against aggressive body exudates and humidity is required. The hydrophilic three-phase pastes or cream pastes show considerable water uptake and fulfil common expectations of pastes to dry the skin.

Absorption↗
PubMed1994

Acitretin biotransformation into etretinate: role of ethanol on in vitro hepatic metabolism.

The aim of this study was to investigate the possible esterification of acitretin into etretinate by using hepatocytes in primary culture from the rat, monkey, dog and man. With rat and human hepatocytes, etretinate was detectable only when ethanol was co-administered with acitretin. With monkey and dog cells, traces of etretinate were found without ethanol addition, but the esterification of acitretin was highly enhanced by ethanol. The metabolic profile was not changed when cells were pre-incubated with ethanol. Therefore acitretin seems to act rather as a substrate than an enzymatic inducer.

Acitretin↗
PubMed1994

Pain assessment after intramuscular injection.

Several parameters (pH, osmotic pressure) influencing the local tolerance of injectable drugs have been well-documented; however, little attention has been paid to pain following an injection--a common problem in clinical practice. A pain questionnaire was used to record pain up to 24 h after a deep ventrogluteal injection. Two groups of healthy volunteers were recruited: the first group (n = 6) received 3 different cotrimoxazole preparations and placebo and the second group (n = 10) received 4 different multivitamin preparations and placebo (double-blind, cross-over). Parameters monitored during and after injection included pain localization (line drawing), pain intensity (visual-analog scale: VAS) and verbal description of pain (pain rating index: PRI). In both groups, the equality of pain (VAS, PRI) induced by the preparations was rejected in all cases (Friedman's test, p < or = 1%). The pairwise comparisons of the groups showed significant differences (p < or = 5%) between various preparations. The correlation (Spearman's rank correlation) between pain parameters VAS and PRI was high. The present investigations have shown that the pain questionnaire is a valuable tool to investigate the subjective pain symptoms during and after the injection of different preparations.

Adult↗
PubMed1993

In vivo skin penetration of acitretin in volunteers using three sampling techniques.

Etretinate and acitretin are given orally to treat psoriasis and various keratinization disorders. Acitretin, the main active metabolite of etretinate, has the pharmacokinetic advantage of being rapidly eliminated, but it shares etretinate's toxicologic profile. Thus a topical delivery of acitretin with no or reduced systemic adverse effects is desirable. To characterize the therapeutic potential of topically delivered acitretin, we quantitatively assessed its percutaneous penetration in healthy human volunteers. Additionally, three skin sampling techniques, the punch biopsy, the shave biopsy, and the suction blister technique, were validated to quantitate acitretin in the skin. The results suggest that topical delivery of acitretin renders skin concentrations which exceed those reported after oral administration of etretinate or acitretin. However, because of possible interlaminate drug contamination, drug localization within a particular skin compartment cannot be determined.

Acitretin↗
PubMed1993

In vivo percutaneous absorption of [14C]acitretin in the hairless guinea pig and in the rhesus monkey.

The oral administration of retinoids such as etretinate and acitretin (Ro 10-1670, CAS 55079-83-9), provides a successful therapeutic approach in various cutaneous diseases characterized by disturbed keratinization, e.g. psoriasis. Nevertheless oral therapy is often associated with systemic adverse effects. This makes a topical form with no or reduced systemic side effects desirable. Direct application of a topical acitretin formulation to the skin might result in therapeutic skin concentrations while minimizing systemic exposure. In the hairless guinea pig and in the rhesus monkey the percutaneous absorption of [14C]acitretin from an isopropylmyristate formulation (160 micrograms acitretin/2.5 cm2/animal) were investigated in vivo. After a 24 h exposure drug concentration in the skin was higher in the hairless guinea pig (620 ng-eq/g wet tissue) than in the rhesus monkey (380 ng-eq/g wet tissue). A similar observation was made comparing the 24 h absorption data determined as amount of drug excreted. The results are compared with in vitro absorption data using skin from the same species.

Acitretin↗
PubMed1993

[Distribution of acitretin in human skin].

Acitretin has recently been introduced for the systemic treatment of dermatologic diseases such as psoriasis and congenital disorders of keratinization. At present, only an oral form of this drug is available. However results from recent studies have shown that considerable drug concentrations can be delivered to the skin by topical administration of acitretin. Based on this data we addressed the question whether the topical administration of acitretin can produce in humans a drug concentration in the skin which exceeds the drug concentration that is found in the skin after multiple oral acitretin dosing and is reported to be clinical effective. Drug concentrations in the skin were investigated under conditions in which the maximum dose that can be administered in a therapeutic situation was applied. Additionally, three different skin sampling techniques, the punch biopsy, the shave biopsy and the suction blister technique were validated to quantitate acitretin in the skin. The drug concentrations in skin after systemic application in a steady state situation were comparable with the drug concentration reached after a single 24 hours topical application of a saturated acitretin/isopropylmyristate formulation. However, no unequivocal effects in psoriasis and disorders of keratinization were observed up to now by the topical administration of acitretin. The inverse drug concentration gradients which are present in the skin, depending on the route of administration, may explain differences in activity. The skin samples in our and other studies were homogenized or dissolved and thus much of the anatomical information is lost. The latter may be most important for the understanding of the local events.

Acitretin↗
PubMed1992

Effect of a new topical cyclosporin formulation on human allergic contact dermatitis.

We studied the effect of a new topical cyclosporin (CS) formulation on the suppression of allergic contact dermatitis. 4 test sites were outlined on the back of healthy male volunteers. For 7 consecutive days, the test sites were treated as follows: #1: CS formulation (10%), #2: placebo formulation, #3: flumethasone pivalate (FP) formulation (0.02%; #4: no treatment. On day 8, we challenged all test sites in the diphenylcyclopropenone (DCP) sensitized individuals. Photographic and clinical documentation was performed daily. 24 h after the DCP skin challenge, a marked redness accompanied by severe itching and slight pain occurred in the test sites pretreated with CS (#1) and placebo (#2). A considerably milder reaction was noted in the untreated test site (#4) and only a faint redness was noted in the test site pretreated with FP (#3). After 36 h, a further increase in the cutaneous reaction was documented in CS and placebo pretreated test sites (#1, 2). In agreement with other workers, topical CS did not suppress experimentally-induced allergic contact dermatitis in man. On the contrary, in CS and placebo pretreated areas (#1, 2), an increased cutaneous reaction was observed. This observation may be explained by the extensive pretreatment with the topical formulation of CS and placebo, which possibly caused a profound perturbation of the stratum corneum, enabling excessive allergen penetration compared to the untreated area with intact stratum corneum.

Administration, Cutaneous↗
PubMed1992

Clinical controversy on the effect of topical ciclosporin: what is the target site?

In recent years attempts have been made to treat T-cell-mediated skin diseases with topical therapeutics. Based on clinical data on the local treatment of recalcitrant erosive lichen planus (LP) with ciclosporin (CS) we discuss in vitro and in vivo studies on percutaneous absorption of CS, drug localization and drug metabolism in the skin as well as clinical data. Clinically relevant immunosuppressive activity depends not only on drug distribution in the target organ skin. The inhibition of T cell response is also dependent upon T cell subsets involved and the activation stage of the T cell. There are different proportions in T cell subpopulations during different evolutional stages of LP. Thus responsiveness to therapy with this drug may depend on the disease activity. Furthermore lymphocyte migration throughout various organs in the body including skin depend on a variety of molecular and cellular interactions. Whether local CS is sufficient to inhibit these interactions or to inactivate already activated T cells remains unclear. Assuming that the T lymphocyte is the target site for CS, local therapy reaches only a small fraction of the T cell population. This may be insufficient, and a systemic inhibition of helper/inducer T lymphocyte function is needed for successful therapy. With CS and with other drugs it seems that percutaneous absorption is not the only key to variable clinical responses to topical therapy.

Administration, Cutaneous↗
PubMed1992

Lack of effect after local treatment with a new ciclosporin formulation in recalcitrant erosive oral lichen planus.

We treated 7 patients with recalcitrant enoral lichen planus (Lp) with a new hydrophilic ciclosporin (CS) formulation during 8 weeks. The preparation with proven in vivo percutaneous absorption was designed for topical use and contained 100 mg CS/g formulation. The patients applied a cumulative daily dose of about 126 mg CS. We did not see the previously reported clinically impressive response with our CS formulation. No CS was detected in the blood of our patients. We conclude that percutaneous absorption of CS is not the key event to the clinical responses. Clinical benefit after CS in enoral Lp seems rather to the clinical responses. Clinical benefit after CS in enoral Lp seems rather to be related to a systemic effect of the drug.

Administration, Topical↗
PubMed1991

Effect of sodium lauryl sulfate-induced skin irritation on in vitro percutaneous absorption of four drugs.

The influence of irritant contact dermatitis on percutaneous penetration was investigated for four 14C-labeled compounds with diverse physicochemical properties: hydrocortisone (HC), indomethacin (IM), ibuprofen (IB), and acitretin (AC). Hairless guinea pigs were pretreated in vivo for 24 h with either 0.5% sodium lauryl sulfate (SLS) to induce irritant contact dermatitis or with water (controls). Twenty-four hours after pretreatment animals were sacrificed. Percutaneous penetration was then measured using in vitro diffusion cells and the removed (pretreated) skin. The following parameters were determined: cumulative amount of compound penetrated, steady state flux, lag time, and permeability coefficient, skin concentration per unit area, and the relative amount of drug remaining in the skin (as a percentage of the cumulative amount of compound penetrated through the skin). SLS pretreatment resulted in moderate irritant dermatitis in all animals and increased in vivo transepidermal water loss 4.5 times. Flux was increased in SLS-pretreated skin as compared with controls for all four compounds, with the greatest enhancement for hydrocortisone (HC) (5.9 times), followed by indomethacin (IM) (4.6 times), ibuprofen (IB) (3.9 times), and acitretin (AC) (3.4 times). Skin concentrations increased to a smaller degree from 1.6 times (IB) and 2.6 times (HC) to 3.4 times (IM). However, AC skin concentrations were not different between the two groups. Thus, percutaneous penetration parameters were equivocally influenced by SLS-induced irritation. Increased skin concentrations were paralleled by even higher increases in flux.

Acitretin↗
PubMed1991

Effect of sodium lauryl sulfate-induced skin irritation on in vivo percutaneous penetration of four drugs.

The influence of sodium lauryl sulfate-induced irritant contact dermatitis on in vivo percutaneous penetration was investigated for four 14C-labeled compounds with diverse physicochemical properties: hydrocortisone (HC), indomethacin (IM), ibuprofen (IB), and acitretin (AC). Hairless guinea pigs were pretreated for 24 h with either 0.5% sodium lauryl sulfate (SLS) to induce irritant contact dermatitis or with water (controls). Twenty-four hours after pretreatment, 450 microliters saturated solutions of HC, IM, IB, or AC in isopropylmyristate were applied to the pretreated skin for 24 h. Systemic absorption was determined by urinary and fecal excretion of compounds. Drug concentrations in stratum corneum (obtained by tape cellophane stripping after decontamination of the application site) and in epidermis/dermis (punch biopsy) were also investigated. Systemic absorption of topically applied drugs (as evaluated by urinary and fecal excretion) in SLS-irritated skin was significantly increased for HC (factor 2.6) followed by IB (1.9 times) and IM (1.6 times) but not increased for AC. However, drug concentrations in the viable epidermis and dermis were 70% lower in SLS-irritated than normal skin for HC, but not different for IB, IM, and AC. Thus, the influence of the state of the skin (irritant dermatitis versus healthy) on percutaneous penetration was different for diverse drugs. The general assumption that percutaneous penetration and drug tissue concentrations were higher in diseased versus healthy skin was not found to be true in our irritated-skin model.

Acitretin↗