Bath-8-MOP-UVA Therapy for Psoriasis / 대한피부과학회지

BACKGROUND: An alternative approach to oral PUVA therapy for psoriasis, psoralen bath plus UVA therapy(bath PUVA therapy) that avoids the adverse effects associated with oral PUVA therapy has increasingly been used during recent years. OBJECTIVE: This study was performed to evaluate the efficacy and safety of bath-8-MOP-UVA therapy in the treatment of psoriasis. METHODS: Twenty patients were enrolled in this study after determination of the minimal phototoxic doses(MPD). We evaluated the total treatment number, duration, final UVA dose and total cumulative UVA dose of bath-8-MOP-UVA therapy to reach grade 4 response and categorized each patient into clearing, improvement, or failure groups based on the therapeutic efficacy. We measured the PASI score at two week intervals. Blood samples were obtained from all twenty patients 2 hours after bath-8-MOP and plasma levels of 8-MOP were quantified by a reverse phase high performance liquid chromatography. RESULTS: The following results were obtained from this study. 1. Phototoxicity testing with bath-8-MOP-UVA elicited mean MPD value of 3.5+/-1.3J/cm2. 2. The mean PASI score at 10 weeks was significantly decreased to 5.8+/-1.3 from baseline PASI score 20.1+/-4.3. 3. Among 20 patients, clearing was shown in 13 patients(65%), 6 patients(30%) were improved and 1 patients(5%) showed failure. 4. In clearing and improvement groups, the mean treatment number, duration, final dose of UVA and total cumulative UVA dose reaching grade 4 were 19.3+/-5.4, 49.9+/-13.5days, 5.2+/-1.3J/cm2 and 68.6+/-30.1J/cm2, respectively. 5. Five patients experienced side-effects. Two patients had intense tan, one withdrawing because of it and the other continued treatment. Three had pruritus that was controlled on oral antihistamines. Phototoxic or other classic adverse effects of oral PUVA therapy, such as nausea, vomiting and headaches, were not observed in any of our 20 patients. 6. All twenty patients had an undetectable plasma 8-MOP level. The lower limit of detection level was 20ng/ml. CONCLUSION: Bath-8-MOP-UVA therapy for psoriasis is a very effective and safe alternative to oral PUVA therapy.

Pharmacokinetic Profiles of Isoniazid and Rifampicin in Korean Tuberculosis Patients / 결핵

BACKGROUND: Isoniazid(INH) and rifampicin(RFP) are the most effective anti-tuberculosis drugs which make the short-course chemotherapy possible. Although prescribed dosages of INH and RFP in Korea are different from those recommended by American Thoracic Society, there has been few study about pharmacokinetic profiles of INH and RFP in Korean patients who receive INH, RFP, ethambutol(EMB) and pyrazinamide(PZA) simultaneously. METHODS: Among the patients with active tuberculosis from Dec. 1997 to July 1998, we selected 17 patients. After an overnight fast, patients were given INH 300mg, RFP 450mg, EMB800mg and PZA 1500mg daily. Blood samples for the measurement of plasma INH(n=15) and RFP(n=17) level were drawn each at 0, 0.5, 1, 1.5, 2, 4, 6, 8 and 12hrs, and urine was also collected. INH and RFP level in the plasma and the urine were measured by high-performance liquid chromatography(HPLC). Pharmacokinetic parameters such as peak serum concentration(Cmax), time to reach to peak serum concentration(Tmax), half-life, elimination rate constant(Ke), total body clearance(CLtot), nonreanl clearance(CLnr), and renal clearance(CLr) were calculated. RESULTS: 1) Pharmacokinetic parameters of INH were as follows: Cmax; 7.63 +/- 3.20 micro gram /ml, Tmax; 0.73 +/- 0.22hr, half-life;2.12 +/- 0.84hrs, Ke;0.83 +/- 0.15hrs-1, CLtot;17.54 +/- 8.89L/hr, CLnr; 14.74 +/- 8.35L/hr, CLr; 2.79 +/- 1.31L/hr 2) Pharmacokinetic parameters of RFP were as follows : Cmax; 8.93 +/- 3.98 micro gram/ml, Tmax;1.76 +/- 1.13hrs, half-life;2.27 +/- 0.54hrs, Ke;0.32 +/- 0.08hrs-1, CLtot;14.63 +/- 6.60L/hr, CLr;1.04 +/- 1.55L/hr, CLnr;13.59 +/- 6.21L/hr. 3) While the correlation between body weight and Cmax of INH was not statistically significant (gamma=-0.514, p value >0.05), Cmax of RFP was significantly affected by body weight of the patients(gamma=-0.662, p value <0.01). CONCLUSION: In Korean patients with tuberculosis, 300mg of INH will be sufficient to reach the ideal peak blood level even in the patients over 50kg of body weight. However, 450mg of RFP will not be the adequate dose in the patients who weigh over 50~60kg.

Comparison of the Concentrations of 8-MOP in both Plasma and Suction Blister Fluid after Oral Ingestion

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.

Pharmacokinetic Study of Isoniazid and Rifampicin in Healthy Korean Volunteers / 결핵

BACKGROUND: Isoniazid(INH) and rifampicin(RFP) are potent antituberculous drugs which have made tuberculous disease become decreasing. In Korea, prescribed doses of INH and RFP have been different from those recommended by American Thoracic Society. In fact they were determined by clinical experience rather than by scientific basis. Even there has been. few reports about pharmacokintic parameters of INH and RFP in healthy Koreans. METHOD: Oral pharmacokinetics of INH were studied in 22 healthy native Koreans after administration of 300mg and 400mg of INH to each same person successively at least 2 weeks apart. After an overnight fast, subjects received medication and blood samples were drawn at scheduled times over a 24-hour period. Urine college lion was also done for 24 hours. Pharmacokinetics of RFP were studied in 20 subjects in a same fashion with 450mg and 600mg of RFP. Plasma and urinary concentrations of INH and RFP were determined by high-performance liquid chromatography(HPLC). RESULTS: Time to reach peak serum concentration (Tmax) of INH was 1.05α0.34 hrs at 300mg dose and 0.98α0.59 hrs at 400mg dose. Half-life was 2.49α0.88 hrs and 2.80α0.75 hrs, respectively. They were not different significantly(p>0.05) Peak serum concentration(Cmax) after administration of 400mg of INH was 7.14α 1.95mcg/mL which was significantly higher than Cmax (4.37α1.28mcg/mL) by 300mg of INH(p0.05). Cmax after administration of 600mg of RFP was 13.61 α3.43mcg/mL which was significantly higher than Cmax(10.12α2.25mcg/mL) by 450mg of RFP(p<0.01). CLtot of RFP at 450mg dose was 7.60α1.34mL/hr. At 600mg dose it was 7.05α 1.20mL/hr which was significantly lower(p<0.05) than by 450mg dose. While CLr was not different among two groups, CLnr at 600mg dose(5.36α1.20mL/hr) was significantly lower than CLnr(6.19α 1.56mL/hr) by 450mg dose(p<0.01). CONCLUSION: Considering Cmax and CLnr, 300mg, of INH and 450mg RFP might be sufficient doses for the treatment of tuberculosis in Koreans. But it remains to be clarified in the patients with tuberculosis.