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At least 217 records · Page 12Linked to original sources
PubMed2005

Decreasing malathion application time for lice treatment reduces transdermal absorption.

OBJECTIVE: Head lice are the most common parasitic infestation in the United States requiring topical treatment with pediculicides. Ovide, the 0.5% malathion formulation used in treatment of head lice requires placement on dry hair for 8-12 h. Malathion, however, is effective at killing lice and nits in 10 min. Our concern of over exposing children to malathion has led us to examine whether significantly more malathion will penetrate transdermally when applied for the recommended 8 h than for a shorter but apparently equally effective period. METHODS: In vitro absorption studies were performed across haired rat skin and human abdominal skin to determine whether reducing malathion application time decreased skin absorption. RESULTS: A 0.5 h exposure caused 0.36+/-0.14% of the donor malathion to penetrate through human skin after 24 h and 2.1+/-0.6% remained in the skin after washing with shampoo. After 8 h of topical applications penetration was approximately three-fold greater (1.02+/-0.41) and 3.4+/-0.5% remained in the skin (p<0.05 versus 0.5 h). The relationship between absorption and exposure time also occurred for haired rat skin (p<0.05). This differential continued for 72 h even after removal of the source. CONCLUSIONS: Significantly less malathion penetrated from Ovide after 0.5 h versus the suggested 8 h application, without decreasing the product's efficacy. Further clinical studies in children are warranted to confirm the efficacy of this shortened application time.

Animals↗
PubMed2000

Automated In Vitro Dermal Absorption (AIVDA): predicting skin permeation of atrazine with finite and infinite (swimming/bathing) exposure models.

The Automated In Vitro Dermal Absorption (AIVDA) HPLC method developed in our laboratory for finite dose tests was developed further for infinite dose swimming/bathing exposure tests and for monitoring skin viability during the permeation assay. Skin absorption of the herbicide atrazine was tested under both finite and infinite dose conditions and the data compared to that obtained using the Bronaugh flow-through cell. Confirmation that skin viability was maintained throughout the AIVDA 24-hr infinite dose tests without phenol was obtained using a novel Radio-HPLC method that was developed to monitor glycolytic 14C-lactic acid formation in 14C-glucose spiked receiver solution. Advantages of the AIVDA method (e.g. rapid, sensitive, versatile, cost-effective analysis) together with its disadvantages (e.g. need for manual dexterity, lack of receiver albumin, compound retention time, limit of sampling interval) are discussed.

Atrazine↗
PubMedDate not supplied

Effects of skin occlusion on percutaneous absorption: an overview.

Skin occlusion produces profound changes, including hydration status, barrier permeability, epidermal lipids, DNA synthesis, microbial flora, and numerous molecular and cellular processes. It often, but not always, increases percutaneous absorption of applied chemicals. This overview focuses on the effect of skin occlusion on percutaneous absorption.

Animals↗
PubMed1993

Effect of hydrophilic and lipophilic vehicles on skin permeation of tegafur, alclofenac and ibuprofen with or without permeation enhancers.

The effects of an ethanol/panasate 800 (tricaprylin) (40/60) system as a lipophilic vehicle, and an ethanol/water (60/40) system as a hydrophilic vehicle, with or without permeation enhancers for in vitro skin permeation and in vivo skin absorption of tegafur, alclofenac and ibuprofen with different lipophilicity, were evaluated. The in vitro and in vivo skin permeability of tegafur, alclofenac and ibuprofen was enhanced by the use of ethanol/panasate 800 (40/60) or ethanol/water (60/40) binary vehicles as a donor composition. However, the two vehicles showed contrastive properties in relation to the extent of permeation enhancement of the three drugs: tegafur > alclofenac > ibuprofen for the ethanol/panasate 800 (40/60) system, and ibuprofen > or = alclofenac > tegafur for the ethanol/water (60/40) system. When lauric acid, as a permeation enhancer, was added to both of the binary vehicles, the in vitro and in vivo skin permeability of three drugs further increased, and the in vivo absorption rate of the drugs from the ethanol/water (60/40) system was larger than that from the ethanol/panasate 800 (40/60) system. In conclusion, it was suggested that the ethanol/panasate 800 (40/60) lipophilic binary vehicle is useful for hydrophilic drugs, and conversely, the skin absorption of lipophilic drugs can be improved by the use of the ethanol/water (60/40) hydrophilic binary vehicle with or without lauric acid as a permeation enhancer.

Animals↗
PubMed1985

Percutaneous absorption of malathion in the guinea-pig: effect of repeated topical application.

The effects of daily repeated topical application and of washing on the percutaneous absorption of malathion have been investigated in guinea-pigs. Skin absorption was determined indirectly by measurement of radioactivity excreted into the urine following topical administration of 14C-labelled malathion, with correction of these values for incomplete renal elimination. Malathion was applied at a concentration of 5 mg/cm2 every 24 hr to the same site on the post-auricular bald area for 15 days. Doses 1, 8 and 15 were radiolabelled. The effect of multiple application and washing was assessed by Newman-Keuls multiple range test for statistical significance. The percutaneous absorption of malathion was 2-3 times higher with washing than without. There was no significant increase (P greater than 0.05) in the percutaneous absorption of malathion with repeated application without washing. These studies suggest that the total penetration of malathion resulting from daily topical dosing without daily washing may be predicted from a single-dose application to the same unwashed site at an equivalent surface concentration, and also that repeated washing with soap and water may significantly decrease the barrier function of guinea-pig skin.

Animals↗
PubMedDate not supplied

Percutaneous absorption of trinitrobenzene: animal models for human skin.

The percutaneous absorption of 1,3,5-trinitrobenzene (TNB) was studied in viable skin from hairless guinea pigs (HGP), Fischer 344 rats and humans. Skin was dermatomed and assembled in flow-through diffusion cells followed by TNB application in either an acetone or a water vehicle. Skin absorption was expressed as the percentage of applied dose absorbed into skin and receptor fluid within 24 h. Rapid absorption of TNB by rodent skin was obtained with both vehicles. For HGP skin, TNB absorption was 72.7+/-5.5% in the acetone vehicle and 82.3+/-4.5% in the water vehicle. For rat skin, TNB absorption was 61.0+/-4.1% (acetone) and 66.5+/-4.1% (water). Absorption of TNB from acetone was significantly reduced (38.0+/-11.0%, P = 0.0118) in human skin, but absorption from water remained high (75.5+/-10.8%). Little TNB remained in skin when a thin (200 microm) dermatome section was used (HGP and human skin). A thicker dermatome section was required (350 microm) with haired rat skin, and 13-21% of the absorbed radioactivity remained in the skin at 24 h. Rodent skin did not simulate satisfactorily the barrier properties of human skin when TNB absorption was reduced by application in a volatile solvent.

Animals↗
PubMed2003

Efficacy and irritancy of enhancers on the in-vitro and in-vivo percutaneous absorption of curcumin.

Curcumin is a predominant compound derived from the rhizomes of Curcuma longa L., and shows antibacterial, anti-inflammatory and antineoplastic activity. The in-vitro and in-vivo skin absorption of curcumin was investigated after application of enhancers using Wistar rat as an animal model. The enhancers selected in this study included terpenes, flavonoids and cholestanol. The irritant profiles of these enhancers were also established by transepidermal water loss (TEWL) and histological observations. Cyclic monoterpenes generally showed stronger enhancement of curcumin permeation than the other enhancers. Modulation of concentration and pretreatment duration of enhancers possibly indicated that the enhancers have varied ability and mechanisms to enhance curcumin permeation. Terpineol produced the highest TEWL values among the enhancers tested, whereas ketocholestanol produced no, or only a negligible, increase in TEWL as compared with control. The results showed that skin disruption and inflammation did not necessarily correspond to the enhancing efficiency of the enhancers.

Administration, Cutaneous↗
PubMed1982

Phloretin sensitive active urea absorption in frog skin.

This report presents evidence for urea active absorption by isolated skin of Rana esculenta. One of the supporting factors of such evidence is that at a low concentration the urea influx is five times greater than the outflux, in the absence of a chemical gradient. The transport shows a saturation kinetics with an apparent Km = 1.33 mM and is inhibited by un uncoupling agent (FCCP). 5 x 10(-4) M Phloretin, added to the external side, markedly inhibits inward urea transport, whereas it is ineffective when added to the serosal fluid. This provides evidence for a phloretin-sensitive mechanism located at the external side of the epithelium. Phloretin stimulates the sodium active transport; the possible coupling of urea and sodium movement is analysed.

Animals↗
PubMed1988

In vitro percutaneous absorption in mouse skin: influence of skin appendages.

Skin appendages are often envisaged as channels that bypass the stratum corneum barrier and are generally thought to facilitate the dermal absorption of topical agents. However, the significance of this transappendageal pathway in percutaneous absorption remains to be assessed experimentally. With the use of a skin organ culture penetration chamber system, the influence of skin appendages on the in vitro permeation of topically applied benzo[a]pyrene and testosterone (5 micrograms/2 cm2) was examined in skin preparations from both haired and hairless mice. Haired mice examined included the C57BL6, C3H, DBA2, Balbc, and Sencar strains and the hairless mice were the HRS and SKH. In all mouse strains examined, the overall permeation of testosterone (greater than 65% of applied dose) 16 hr following in vitro topical application was greater than that of benzo[a]pyrene (less than 10%). No strain differences were observed with respect to the percutaneous permeation of testosterone; however, percutaneous permeation of benzo[a]pyrene in the haired mice (7-10% of applied dose) was higher than that in the hairless mice (2%). In an in-house derived mouse strain which showed three phenotypic variants due to hair densities, the permeability to both compounds was highest in the skin of the haired phenotype (testosterone 67%, benzo[a]pyrene 7%), lowest in the hairless phenotype (35 and 1%, respectively) and intermediate in the fuzzy-haired animal (57 and 3%, respectively). Examination by fluorescence microscopy of cryosections of skin, prepared 1 hr after topical benzo[a]pyrene, showed areas of intense fluorescence deep within the nonfluorescing dermis of skin from the haired phenotype. These fluorescent areas were correlated with follicular ducts and sebaceous glands. In contrast, skin from the hairless phenotype showed no evidence of fluorescence in the dermis and intermediate was the fluorescence observed in the skin from the fuzzy-haired animal. These observations showed that transappendageal penetration could contribute significantly to the overall skin absorption of topical agents. They also suggest that regional distribution of skin appendages could influence the percutaneous fate of topically applied chemicals.

Animals↗
PubMed1992

Absorption of amorolfine through human nail.

The percutaneous absorption of a new antifungal agent, amorolfine, has been measured through both skin and nail using an in vitro technique. Application of a 5% concentration in either an ethanol or methylene chloride lacquer resulted in permeation rates through nail in the range of 20-100 ng/cm2/h and somewhat higher through skin. Absorption was greater from the methylene chloride lacquer than the ethanol lacquer.

Absorption↗
PubMed1997

Percutaneous absorption of vanilloids: in vivo and in vitro studies.

The percutaneous absorption of three highly lipophilic analogs of capsaicin--vanillylnonanamide (VN), olvanil, and NE-21610--was measured in vivo in the CD:VAF rat, and in vitro through excised CD: VAF and SkH:Fz rat skin and human cadaver skin. Absorption and skin metabolism were monitored by radiolabel techniques. The rank order of penetration in all species was VN > olvanil > NE-21610, in accordance with that expected from their physical properties. Rat skin was more permeable than human skin by factors ranging from 4 to 8 for VN, 10 to 20 for olvanil, and approximately 10 to 100 for NE-21610. All three compounds were extensively metabolized during passage through fresh SkH:Fz rat skin, with the primary route of degradation for at least two of the compounds involving hydrolysis of the amide bond (the metabolites of NE-21610 were not identified). For the in vitro studies a range of receptor solutions was employed to determine a set of conditions that best mimicked in vivo absorption. The results with phosphate-buffered saline containing a preservative and 1-6% polyoxyethylene-20 oleyl ether (Oleth-20) were in good agreement with in vivo results for all three compounds for periods up to 24 h post-dose; after this time, in vivo absorption rates declined but in vitro rates remained relatively constant. Buffered saline or saline containing 0.5% bovine serum albumin led to marked underestimates of in vivo penetration for olvanil and NE-21610, whereas a 1:1 ethanol: water solution led to gross overestimates of the in vivo absorption rates for all three compounds.

Animals↗
PubMed1991

Influence of two vehicles for zinc oxide on zinc absorption through intact skin and wounds.

The zinc absorption from zinc oxide applied on intact and on wounded skin were compared using two vehicles: one containing gum rosin and the other containing hydrocolloids. After treatment of intact human forearm skin for 48 h, the zinc concentration was more than two-fold higher in the epidermis and interstitial fluid beneath the rosin vehicle than beneath the hydrocolloid vehicle. Systemic absorption of zinc through full-thickness rat skin wounds treated with zinc oxide increased significantly, however, with the use of the hydrocolloid vehicle. In vitro experiment indicated that the solubility of zinc oxide in buffered saline (pH 7.4) increased in the presence of hydrocolloids. The study, thus, indicates that rosin in combination with zinc oxide enhances the transport of zinc through intact human skin, and that hydrocolloids promote the zinc absorption through wounds.

Adult↗
PubMed2000

Comparative in vitro-in vivo percutaneous absorption of the pesticide propoxur.

In vitro and in vivo skin absorption of the pesticide propoxur (2-isopropoxyphenyl N-methyl carbamate, commercially Baygon(TM) and Unden (TM); log Po/w 1.56, MW 209.2) was investigated. In vivo studies were performed in rats and human volunteers, applying the test compound to the dorsal skin and the volar aspect of the forearm, respectively. In vitro experiments were carried out in static diffusion cells using viable full-thickness skin membranes (rat and human), non-viable epidermal membranes (rat and human) and a perfused-pig-ear model. Percutaneous penetration of propoxur in human volunteers was measured by analysis of its metabolite (2-isopropoxyphenol) in blood and urine; in all other studies radiolabeled propoxur ([ring-U-(14)C]propoxur) was used. In order to allow for direct comparison, experimental conditions were standardized with respect to dose (150 microg propoxur per cm(2)), vehicle (60% aqueous ethanol) and exposure time (4 h). In human volunteers, it was found that approximately 6% of the applied dose was excreted via the urine after 24 h, while the potential absorbed dose (amount applied minus amount washed off) was 23 microg/cm(2). In rats these values were 21% and 88 microg/cm(2), respectively. Data obtained in vitro were almost always higher than those obtained in human volunteers. The most accurate in vitro prediction of the human in vivo percutaneous absorption of propoxur was obtained on the basis of the potential absorbed dose. The absorbed dose and the maximal flux in viable full-thickness skin membranes correlated reasonably well with the human in vivo situation (maximal overestimation by a factor of 3). Epidermal membranes overestimated the human in vivo data up to a factor of 8, but the species-differences observed in vivo were reflected correctly in this model. The data generated in the perfused-pig-ear model were generally intermediate between viable skin membranes and epidermal membranes.

Animal Testing Alternatives↗