In order to measure the MPD with 8-methoxypsoralen, we selected 49 Korean healthy male vlunteers without phototoxic or photosensitive dermatoses. They were divided to 3 groups (Immediate; group 1, 1 hour; group 2, 2 hours', group 3) according to the waiting time, intervals of application of photosensitizer a,nd UVA:irradiation. The reaults were summarized as follows: 1. MPDs of group 1 had no clinical significance. 2, MPDs of group 2 were more than those of group '3 independently of application methods of photosensitizer. 3. In the cases of topical application of 8-MOP, MPDs of group 3 according to reading interval (24 hours, 48 hours and 72 hours after UVA irradiation) were 3.4+/-2.9 J/cm2, 1.9+/-l.5 J/cm' and l. 7+1, 2/cm, respectively. 4 In the cases of oral administration of 8-MOP, MPDs of group 3 according to reading; interval as topical application of 8-MOP were 7.1+/-2.3 J/cm, 4.4+/-1.1 J/ cm2 and 4.2+/-l.2 J/cm2, respectively. 5 MPL)s accarding to the skin types as follows; (waiting time; 2 hours, read- ing interval; 48 hours) a. In the case of topical application of 8-MOP, MPDs of the skin type ]II, 1V and V were 0.9+/-0.5 J/cm2, 1.8+/-1.1 J/cm2 and 3.0+/-l.3 J/cm2 respectively. b. In the case of oral administration of 8-MOP, MPDs of skin type g, W and were 3.5+/-1.1 J/cm2, 4.7+/-1.3 J/cm2 and 6.9+/-l.8 J/cm2, respectively.
Administration, Oral ; Humans ; Male ; Methoxsalen ; Skin ; Skin Diseases

The skin concentrations of 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), and 4, 5', 8-trimethylpsoralen (TMP) were studied in the guinea pig following oral administration and bathing. The skin concentration of phototoxic drugs after oral administration peaked at 1.5 hours, and the concentration of 8-MOP was 3.5 times greater than that of 5-MOP. The skin concentration of TMP was not detected in our study (limit of sensitivity 5ng/ml). The skin concentrations of phototoxic drug after bathing decreased in the order of 5-MOP, TMP, and 8-MOP
Administration, Cutaneous ; Administration, Oral ; Animal ; Guinea Pigs ; Methoxsalen/administration & dosage/*analysis ; PUVA Therapy ; Skin/*chemistry ; Support, Non-U.S. Gov't ; Trioxsalen/administration & dosage/*analysis

BACKGROUND: The value of plasma concentration of 8-Methoxypsoralen(8-MOP) in the supervision of photochemotherapy has been recognized. However, plasma levels of 8-MOP were not proportionate to the degree of PUVA induced erythema and couldn't alone predict the degree of PUVA induced erythemal reaction. We made a speculation that the degree of PUVA induced erythema might correlate better with skin tissue levels of 8-MOP than plasma levels. Suction blister fluid(SBF) has been known to represent tissue fluid in the skin. So we per-formed a study of comparison of 8-MOP concentrations in both plasma and SBF. OBJECTIVE: Our purpose was to evaluate the correlation of the concentrations of 8-MOP in plasma and SBF 2 hours after oral administration of 0.6 mg/kg of 8-MOP. METHODS: Twenty six patients, aged between 16 and 50 years, undergoing suction blister surgery for vitiligo treatment, participated in this open study. Single oral doses of 0.6 mg/kg of body weight of 8-MOP were taken. Blood samples(5ml) and SBF(2ml) were collected at 2 hours after the drug administration, and 8-MOP concentration in plasma and SBF were quantitated by reverse phase high-performance liquid chromatography (HPLC). RESULTS: 8-MOP concentrations in plasma and SBF ranged from 18 to 545 ng/ml and 8 to 179 ng/ml, respectively. On the analysis of linear regression, a close-relation could not be observed between two SBF levels; measured and predicted values which were calculated from measured plasma and SBF concentrations (r²=0.583, P < 0.001). CONCLUSION: The correlation of plasma and SBF concentrations of 8-MOP is weak. So, SBF levels of psoralen are recommended for the study of PUVA erythemal reactions.
Administration, Oral ; Blister* ; Body Weight ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Eating* ; Erythema ; Ficusin ; Humans ; Linear Models ; Methoxsalen* ; Organization and Administration ; Photochemotherapy ; Plasma* ; Skin ; Suction* ; Vitiligo

AIMTo investigate the penetration kinetics of xanthotoxin in human skin and stratum corneum.

METHODSThe penetration experiments were accomplished by the deposit of ethanolic xanthotoxin solution onto human skin and stratum corneum mounted on Franz cells. The diffused xanthotoxin in the receptor solution (1.4% human serum albumin) and the retained amount in the skin and in the stratum corneum after 24 h exposure were quantified by using high performance liquid chromatography.

RESULTSXanthotoxin flux was increased with the concentration deposited onto the human skin, and when the concentration is above 2.5 mg x mL(-1), there is no influence on the xanthotoxin flux. Similar results were obtained from the stratum corneum. And the peak time for the flux in the stratum corneum was preceded about 6 h earlier than that of the whole human skin. The retained xanthotoxin amount after 24 h exposure in the skin and in the stratum corneum increased according to the concentration deposited and has the tendency to saturate. The lag time of ethanolic xanthotoxin solution in the whole human skin is significantly higher than that in the stratum corneum (P < 0.05).

CONCLUSIONThe characteristics of penetration kinetics of xanthotoxin will provide the information for concentration choice of topical formulation and give a reference for ultra violet A (UVA) irradiation time confirmation.

Administration, Cutaneous ; Dose-Response Relationship, Drug ; Epidermis ; metabolism ; Female ; Humans ; In Vitro Techniques ; Methoxsalen ; administration & dosage ; pharmacokinetics ; Middle Aged ; Photosensitizing Agents ; administration & dosage ; pharmacokinetics ; Skin ; metabolism ; Skin Absorption ; Time Factors

The beneficial effects of sunlight and ultraviolet light for the treatment, of psoriasis vulgaris has long been recognized. Parrish et al were the first to introduce a controlled light source, which allowed the delivery of a known quantity of light energy to the patients skin after the patient had ingested a photosensitizer, 8-methoxypsoralen (methoxsalen) two hours previous to UVA exposure. This successful treatment has become known as PUVA (psoralen and UVA). PUVA photochernotherapy denotes a systemic approach that is based on the interaction of light and a photoactive drug. Parrish et al have described successful treatment of psoriasis with PUVA and other investigators alI over the world have confirmed their beneficial results. The rationale of photochemotherapy in psoriasis is the inhibition of the increased DNA synthesis within the psoriatic lesions by the interaction of psoralen molecule and light energy in the UVA range(320-400nm). The present study was undertaken to evaluate the therapeutic effectiveness of PUVA photochernotherapy combining orally administered methoxsalen and UAA exposure using Dermatron UVA phototherapy system in patients with wi5espread psoriasis. A total of 15 patients with psoriasis over more than 30% of their bodies were selected at the department of dermatology, National Medical Center through March 1978 to September 1978. Oral administration of methoxsalen, 20 to 50 mg doses according to body weight, was followed by exposure to a high-intensity longwave ultraviolet light emitting a continuous spectrum between 320 and 400nm (peak emission, 350 - 365nm). Initial UVA exposure times were based on each patients minimal phototoxicity dose (MPD) and exposure times were increased at each treatment by 1 - 2 minutes to maintain minimal erythema. Frequency of treatment was two to three times weekly. Once the psoriatic lesions had, cleared completely the patient was placed on a maintenance schedule. If psoriasis recurred the frequency of treatment was increased. The results were as follows: l. 5 patients were dropped out due to unknown reasons. 2. 7 cases showed clearing of over 95, of the lesions (Response 5'). Mean number of PU VA therapy was 16. 7. During 1 4 months follow-up period, 4 cases remained free of psoriasis but 3 cases couldn't be followed. 3. Immediate side effects of PUVA were temporary and generally mild. No significant changes in laboratory screenings were noted. Side effects of therapy included transient nausea(33.3%), dizziness(26.7%), erythema.(66.7%), pruritus (60%), increased pigrnentation(100 %). 4. Comparison of pre-and post-PUVA therapy in biopsy specimens by light microscopy revealed histologic improvement evidenced by diminished acanthosis and parakeratosis, and regeneration of granular layers in all of 8 cases. Glycogen accumulation in the affected epiderrnis was significantly decreased or absent after PUVA therapy in all cases.
Administration, Oral ; Appointments and Schedules ; Biopsy ; Body Weight ; Dermatitis, Phototoxic ; Dermatology ; DNA ; Erythema ; Ficusin ; Follow-Up Studies ; Glycogen ; Humans ; Mass Screening ; Methoxsalen ; Microscopy ; Parakeratosis ; Photochemotherapy* ; Phototherapy ; Pruritus ; Psoriasis* ; PUVA Therapy ; Regeneration ; Research Personnel ; Skin ; Sunlight ; Ultraviolet Rays