Penetration of trioxsalen into skin from trioxsalen baths.
Explore the source record for details and available documents.
Baths↗
SEARCH · Search PubMed
Results for “Trioxsalen”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Shower PUVA: a novel variant of photochemotherapy. Distribution of photosensitivity and accumulation of trioxsalen in the skin.
Shower PUVA is a new variant of photochemotherapy suitable for therapy of various skin disorders. Psoralen, e.g. trioxsalen-containing water recirculates in a closed shower system and wets the skin continuously. After showering, whole-body UVA irradiation (320-400 nm) is performed. In order to prove the equal distribution of photosensitivity in vivo minimal phototoxic dose (MPD) was determined in different skin areas of healthy individuals. Additionally, we investigated the accumulation of trioxsalen in psoriasis lesions under the conditions described by quantifying psoralen in scales collected after showering. In a randomized study 20 healthy volunteers (skin type I-III) took showers for 5 and 10 min in trioxsalen (0.27 mg/l)-containing water at 37 degrees C. Immediately afterwards, MPD was tested on the inside of the upper arms and on the buttocks by using a polychromator light source (315-400 nm). The applied UVA doses were 0.06-0.75 J/cm(2) with steps of 0.125 J/cm(2). MPD was evaluated after 72 h. Equal distribution of photosensitivity was defined as equal MPD on the insides of the upper arm and the buttocks (+/-0.125 J/cm(2)). Skin scales of 21 patients with psoriasis were collected by scratching after showering with trioxsalen-containing water (0.27 mg/l) for 5 min. For quantification of trioxsalen in the scales HPLC was performed. An equal distribution of photosensitivity was achieved in 70% (14/20) cases after 10-min showering in trioxsalen-containing water. Showering for 5 min only revealed a 30% (6/20) rate of equal distributed photosensitivity. After 10-min shower time MPD was 0.325 J/cm(2) (median; range: 0.06-0.625 J/cm(2)). The average amount of trioxsalen found in the scales was 2.03 ng/mg scales (range: 0.38-7.2 ng/mg). For shower PUVA using trioxsalen, 10 min shower time is recommended to achieve sufficient distribution of photosensitivity on the skin. Clinical efficacy of shower PUVA can be explained by skin accumulation of trioxsalen which enters from the aqueous phase into the upper skin layers in detectable amounts. This is the first report demonstrating the efficacy of shower PUVA which in short shower time allows an uptake of psoralen by the skin.
Adult↗
Plasma concentrations after bath treatment and oral administration of trioxsalen.
An analytical method comprising homogenous extraction and determination by gas chromatography mass spectrometry has been developed for the quantitation of trioxsalen in plasma. The limit of sensitivity of the method has been 2 ng/ml of trioxsalen. The method was used to monitor concentrations of trioxsalen in plasma after a 40 mg oral dose or after trioxsalen bath treatment. The concentrations in plasma after oral administration did not exceed 3 ng/ml, while in 2 patients after bath treatment trioxsalen could be determined (2-3 ng/ml). The low plasma concentrations found throw light on the poor UV-sensitizing properties found after oral trioxsalen therapy.
Administration, Oral↗
Trioxsalen bath plus UVA treatment of psoriasis. Plasma concentration of the drug and clinical results.
Forty-five patients with psoriasis were treated with trioxsalen bath plus UVA. Good or excellent results were obtained in 34 (67%) of the 51 treatments. Trioxsalen plasma concentrations were determined at different stages of the treatment in 10 patients 1 hour after trioxsalen bath, and in 11 patients undergoing treatment for vitiligo 2 hours after ingestion of 0.6 mg trioxsalen per kilogram body weight. The determinations were performed using the glass capillary, gas chromatography, mass spectrometry method, reaching a sensitivity of greater than or equal to 25 pg/ml. The trioxsalen plasma concentrations varied between 12.5 and 0.27 ng/ml after oral ingestion and between approximately 9 ng/ml and less than 25 pg/ml after bath application.
Adolescent↗
Comparison of the carcinogenic potential of trioxsalen bath PUVA and oral methoxsalen PUVA. A preliminary report.
BACKGROUND AND DESIGN: There is an increasing concern about the long-term carcinogenic effect of oral psoralen with long-wave UV radiation in the A range (PUVA). Most follow-up investigations indicate a definite risk of squamous cell carcinoma of the skin with long-term PUVA treatment. In a recently published study of 4799 Swedish patients who had received PUVA, it was noted that 833 patients who had received trioxsalen bath or oral trioxsalen did not show any increased risk of skin cancer in contrast to oral methoxsalen. This finding has been further investigated in this study. We compared four dermatologic university clinics in Sweden with regard to the carcinogenic potential of the PUVA regimen used. One clinic used trioxsalen bath PUVA exclusively and the other three used oral methoxsalen. Information on their PUVA-treated patients was collected and linked with information from the Swedish Cancer Registry to identify individuals with squamous cell carcinoma of the skin. RESULTS: A total of 18 squamous cell carcinomas of the skin were reported in 2975 PUVA-treated patients until 1987. The expected number was 3.1. The center using bath PUVA only had no increased risk of squamous cell carcinoma of the skin in contrast to the three centers using oral methoxsalen-PUVA. The increased risk for male subjects from those centers varied from six to 13 times that in the general population, but for female subjects a significant increased relative risk was found only at one center. CONCLUSION: In this preliminary report, PUVA treatment with trioxsalen bath seems to be less carcinogenic than the oral dosage. However, differences in the patient populations might also have affected the outcome of the study. More information on this field is needed.
Administration, Oral↗
Determination of trioxsalen in human plasma in the picogram range by glass capillary gas chromatography mass spectrometry.
Two methods based on glass capillary gas chromatography mass spectrometry have been developed for quantitative determination of trioxsalen, a photosensitizing drug, in human plasma. One employs the extraction of trioxsalen and deuterated internal standard from plasma with dichloromethane and purification of the extract by high pressure liquid chromatography before analysis by selected ion monitoring at low resolution. In the other procedure the raw hexane extracts are analysed by selected ion monitoring at medium resolution. Both methods can be used to determine trioxsalen over the range 25 pg ml-1 to 2 ng ml-1, which corresponds to the range of plasma concentration present after application of trioxsalen as bath.
Chromatography, Liquid↗
Cancer incidence among Finnish patients with psoriasis treated with trioxsalen bath PUVA.
BACKGROUND: Systemic methoxsalen PUVA increases nonmelanoma skin cancer risk in a dose-dependent manner, whereas trioxsalen bath PUVA treatment has been suggested to be less carcinogenic. OBJECTIVE: Our purpose was to study the carcinogenicity of topical trioxsalen PUVA. METHODS: We performed a record linkage study of 337 male and 190 female patients with psoriasis treated with trioxsalen bath PUVA during the period 1977 to 1988 and the Finnish Cancer Registry (cancer incidence in the period 1977 to 1993). The mean follow-up period per person was approximately 11 years. Data on the total cumulative UVA dose and other potentially carcinogenic treatments were collected from the patients' files. The standardized incidence ratio (SIR) was calculated, in which the expected number of cases was based on the national cancer incidence rates. RESULTS: During the follow-up, 26 cancer cases were observed in the cohort versus 30 expected (SIR, 0.88; 95% confidence interval [CI], 0.57-1.28). The only primary sites showing high SIRs were cancer of the kidney (SIR, 3.56; 95% CI, 0.97-9.10) and non-Hodgkin's lymphoma (SIR, 2.94; 95% CI, 0.36-10.6). There was only one case of nonmelanoma skin cancer; the expected number was 0.8 (SIR, 1.26; 95% CI, 0.03-7.04). The average cumulative UVA dose was 65 J/cm2; 40 patients had received more than 200 J/cm2. The average number of treatments was 112; 65 patients had received more than 200 treatments. CONCLUSION: No excess of squamous cell carcinoma of the skin was found in patients treated with trioxsalen bath PUVA. However, because of the small size of the cohort, only a sevenfold excess risk can be excluded. The possible associations between psoriasis or its treatment and kidney cancer and lymphoma need to be studied further in larger series.
Adolescent↗
Trioxsalen bath PUVA did not increase the risk of squamous cell skin carcinoma and cutaneous malignant melanoma in a joint analysis of 944 Swedish and Finnish patients with psoriasis.
It has been suggested that trioxsalen bath and ultraviolet (UV) A (PUVA) is associated with a very low or no risk of non-melanoma skin cancer, but the numbers of patients in individual studies have been limited. In order to attain statistically relevant information about the cancer risk associated with trioxsalen bath PUVA, two follow-up studies were combined and the joined cancer incidence was analysed among 944 Swedish and Finnish patients with psoriasis. The mean follow-up time for skin cancer was 14.7 years. Standardized incidence ratios (SIR) were calculated as a ratio of observed and expected numbers of cases. The expected numbers of cases were based on the national cancer incidence rates in the respective countries. There was no excess of squamous cell skin carcinoma [SIR 1.1, 95% confidence interval (CI) 0.2-3.2] or malignant melanoma (SIR 0.9, 95% CI 0.1-3.2) in the combined cohort. Basal cell skin carcinoma was not studied. The incidence of all non-cutaneous cancers was not increased (SIR 1.1, 95% CI 0.8-1.4). A threefold excess risk of squamous cell skin carcinoma after trioxsalen bath PUVA could therefore be excluded, which is a markedly lower risk than that associated with oral 8-methoxypsoralen PUVA. The result needs to be confirmed in a future follow-up, however, as the number of patients with high PUVA exposures was low.
Adolescent↗
Treatment of psoriasis with trioxsalen baths and dysprosium lamps.
Photochemotherapeutic treatment of psoriasis with trioxsalen baths (0.5 mg/1) for 15 minutes followed by irradiation with dysprosium lamps (Osram HQI-TS) healed or nearly healed the psoriatic lesions in 18 patients within 3-5 weeks. A control area treated with the Ingram method showed a slower healing in 9 of these patients. Methoxsalen bath was not as effective in healing at the concentration used (1 mg/l). The bath method is easy to administer and cosmetically acceptable. Sensitisation to light is maximal immediately after the bath and disappears more quickly than after painting with an alcoholic trioxsalen solution. By using baths, there is less risk of accidental burns or uneven pigmentation than with the often time-consuming local application of psoralen solutions. Toxic systemic effects, which are possible with oral treatment, are less apt to occur. The dysprosium lamps give high intensity in the UV-A region. Exposure times of 10 seconds to 8 minutes are effective in the treatment of psoriasis, where both the UV-B region itself and the UV-A in combination with trioxsalen have psoriasis-healing properties.
Adolescent↗
[A preparation of short DNA chains synthesized in vivo after introduction into DNA from live cells of trioxsalen crosslinks is not enriched by replication initiation regions].
The experiments undertaken in order to verify the trioxsalen-crosslinking method suggested by Russev and Vassilev for isolation of eukaryotic replication origins are described. It was found that the preparation of viral DNA isolated by the above mentioned method from CV-1 cells lytically infected with SV40 was not enriched in sequences including SV40 replication origin. The hybridization pattern of DNA preparation isolated by the trioxsalen-crosslinking procedure from chicken erythroblastosis cells with the cloned fragments of globin gene domain was found to be identical to those of the total DNA probe. The DNA fraction enriched in replication origins was isolated from the same cells with the aid of nascent DNA strand extrusion method by Zannis-Hadjopoulos et al. The hybridization pattern of this DNA fraction with the cloned fragments of chicken alpha-globin gene domain was different from those of total DNA. Taking together, the results of our experiments demonstrate that trioxsalen-crosslinking procedure does not lead to the isolation of replication origins from the objects studied in the present investigation.
Animals↗
Phototoxicity of topical trioxsalen.
The phototoxic properties of topical trioxsalen preparations were studied in 73 test subjects. A W/O emulsion base was superior to petrolatum, O/W emulsion, double emulsion and carbowax. The optimal interval between application of the drug and UVA irradiation varied between 40 and 60 min for both cream and ointment bases. An occlusive dressing greatly enhanced the phototoxic effect of the drug. The skin lost photosensitivity in 4 hours when the preparations were removed from the skin 45 min after the application. For clinical use a proper concentration of trioxsalen in emulsion bases was 0.01-0.1%. Both W/O and O/W emulsion bases with 0.01% trioxsalen locally applied gave moderate or good clinical results in 16 psoriatics and in 4 patients with lichen planus, W/O emulsion being better in this respect.
Administration, Topical↗
Comparative treatment of psoriasis with UV-light, trioxsalen plus UV-light, and coal tar plus UV-light.
Areas within psoriasis plaques have been treated with UV-light alone, trioxsalen plus UV-light, and coal tar (liquid carbonis detergens) plus UV-light, using the 313, 365 and 405 nm wavelength bands in various doses. With the 313 nm band, the same degree of healing was obtained with all three types of treatment. With the 365 nm band, no healing was achieved with UV-light alone, but healing did occur with UV-light when the skin was sensitized with trioxsalen. Coal tar itself has a certain healing effect on psoriasis but the effect is so markedly enhanced by light of the 365 nm band that the healing is comparable to that obtained with the 313 nm band. No healing was seen with light of the 405 nm band. The patients who were healed with the 313 nm band alone, also healed with trioxsalen or coal tar plus UV-light of the 365 nm band. With each method there is an individual optimal light dose of 1--2 MED that gives healing.
Coal Tar↗
Trioxsalen bath plus UVA effective and safe in the treatment of psoriasis.
Seventy-four patients with psoriasis were treated using a trioxsalen bath (50 mg/150 l of water) and long wave ultraviolet light (UVA) given in an ordinary PUVA-cabin. Good or excellent results were observed in 92% of the patients in the initial phase and in 63% during the maintenance treatment. Because of local side-effects the therapy was discontinued in two patients. One of them developed contact hypersensitivity to trioxsalen and the other developed blisters with such low doses of UVA that it was difficult to maintain the proper dose. The therapy was started with 0.28 J/cm2 of UVA and after an average of 18 treatments, when the average dose was 1.70 J/cm2, the patients were moved to maintenance treatment which took place at 1--4 week intervals. The therapy was well tolerated and cosmetically very acceptable. The final tan was even on all but the face, which remained untanned.
Adolescent↗
Long-term safety of trioxsalen bath PUVA treatment: an 8-year follow-up of 149 psoriasis patients.
A thorough clinical follow-up study with regard to the occurrence of degenerative skin changes and cutaneous carcinomas was undertaken in 1982 in 149 patients with moderate to severe psoriasis treated with PUVA baths (trioxsalen + UVA). The PUVA treatment had been commenced between 1974 and 1978. With trioxsalen baths a high sensitivity to UVA is obtained. The initial UVA dosage is therefore as low as 0.04-0.08 J/cm2 and in the majority of the patients the maximum daily dose was about 1.0 J/cm2. The accumulated UVA dosage was low. Thus 89% of the patients had received less than 50 J/cm2 in 5-8 years of bath PUVA treatment. No degenerative skin changes were found on PUVA-exposed skin that were not also seen on the facial skin not exposed to PUVA. Two patients showed mild mottling of exposed skin. Otherwise no PUVA-related degenerative changes were observed. No carcinomas were found on bath PUVA-treated skin.
Adult↗
The effect of PUVA on langerhans cells in rat oral epithelium photosensitized with systemic methoxsalen or topical trioxsalen.
BACKGROUND/PURPOSE: Ultraviolet-A radiation (UVA) of the oral mucosa after photosensitization with either systemic methoxsalen (8-MOP) or topical trioxsalen (TMP), i.e. mouth-PUVA, has been reported to be successful in the treatment of oral lichenoid lesions. In the case of PUVA treatment of skin disorders, local immune suppressive effects have been demonstrated, and the antigen presenting epithelial Langerhans cells (LCs) have been shown to be especially sensitive to ultraviolet treatments. Our aim was to compare the photobiological effects of PUVA in oral mucous membrane (OMM) using topical TMP or systemic 8-MOP photosensitization. METHODS: Rat OMM photosensitized with topical TMP or systemic 8-MOP was treated with PUVA using UVA doses of 1-8 J/cm2. The LCs were demonstrated in epithelial sheets of the treated OMM with ATPase staining. RESULTS: Both treatments caused a sim ilar, dose-dependent depletion of ATPase-positive LCs, with a maximal depletion of 80% or 73% with 8 J/cm2 at 2 days after irradiation as photosensitized with TMP or 8-MOP, respectively. This contrasts with earlier published findings in human skin, where topical TMP is an order of magnitude greater a sensitizer than 8-MOP, and PUVA-induced depletion of LCs occurs maximally 5 days after irradiation. CONCLUSION: The depletion of LCs of rat OMM after PUVA treatment is greater using topical TMP compared to systemic 8-MOP, but the difference is significantly smaller than reported earlier in human skin.
Administration, Oral↗
Bath PUVA--an investigation of the distribution of trioxsalen (TMP) and 8-methoxypsoralen (8-MOP) in bathwater.
Trioxsalen (TMP) bath PUVA avoids the side effects of nausea and headache associated with oral 8-methoxypsoralen (8-MOP) treatment and allows shorter irradiation times that can be advantageous in some patients. However we noted that a number of patients developed unusual patterns of phototoxic burning. We thought that this was related to an uneven distribution of the TMP in the bathwater and for this reason, a study of bath water TMP concentrations achieved using different TMP preparations was undertaken. The distribution of 8-MOP in an 8-MOP bath was also measured for comparison. Our results confirm that an uneven distribution of TMP is achieved using TMP capsules or suspension and would explain our observed patterns of burning. With an ethanolic solution of TMP, or the commercial equivalent Tripsor, or with Puvasoralen-8 (an 8-MOP preparation), a homogeneous psoralen distribution is achieved, and they are therefore preferable for use in bath PUVA.
Administration, Cutaneous↗
Trioxsalen in the presence of UVA is able to induce nuclear factor kappa B binding activity in HaCaT keratinocytes.
It has been described that treatment of cells with high dose psoralen and UVA induce the production of reactive oxygen species (ROS) leading to DNA damage. Transcription factor nuclear factor kappa B (NFkappaB) plays a crucial role in regulating not only cell growth but also cell differentiation, and ROS seem to be partly involved in these mechanisms. The aim of this research was to find out the effect of a combined treatment with trioxsalen (TMP)/UVA on NFkappaB binding activity in HaCaT keratinocytes. HaCaT keratinocytes were treated with 27 microg/l TMP. This concentration did not affect the proliferation rates, nor was it toxic, as shown by cytotoxicity assays. After treatment with TMP with or without UVA (1 J/cm(2)), NFkappaB binding activity in nuclear protein extracts was measured by electrophoretic mobility shift assays. The effect on cytokines and cytokine receptor genes was investigated using cDNA expression arrays. An inhibitory effect on NFkappaB binding activity was found between 30 and 60 min after TMP supplementation of the culture media. UVA irradiation induced a 2-fold increase in NFkappaB binding activity in TMP supplemented HaCaT keratinocytes compared with the non-irradiated control. In addition, NFkappaB binding activity was higher after UVA irradiation with TMP than in UVA irradiated cells in the absence of TMP. TGF-alpha, IL-1R, IL-2Ralpha, IL-12beta and PDGF expression was induced by UVA. However, all of them except PDGF were inhibited by combined TMP/UVA treatment. Using an inhibitor of NFkappaB activation, we found out that under these conditions, these cytokines or cytokine receptor genes are apparently not regulated by NFkappaB. Our results indicate that a combined TMP/UVA treatment of HaCaT keratinocytes induces NFkappaB binding activity, and that this is a synergistic effect. The investigated cytokines, and cytokine receptor genes do not seem to be NFkappaB regulated; however, TMP shows anti-inflammatory capacities in vitro.
Cell Division↗
Long-term local trioxsalen photochemotherapy in psoriasis.
Good results were achieved in psoriasis with trioxsalen baths and UVA in 92% of 158 patients during initial treatment and in 83% of 139 patients during long-term treatment. Grade I-II local burns were encountered in about 7% of the patients. In addition, itchy skin pain was experienced by 2 patients, and in both of these the therapy was discontinued. Neither skin malignomas nor other serious side effects were seen.
Administration, Topical↗