Therapeutic effects of CO2 laser therapy of linear nevus sebaceous in the course of the Schimmelpenning-Feuerstein-Mims syndrome.

The Schimmelpenning-Feuerstein-Mims (SFM) syndrome is a rare phakomatosis which comprises a nevus sebaceous of Jadassohn, seizures and developmental delay associated with a wide spectrum of extracutaneous abnormalities including neurological, skeletal, ocular, cardiovascular and urogenital defects. We are presenting a case of an 18-year-old patient with systemic features of the SFM syndrome and an extensive linear nevus sebaceous partially removed with a carbon dioxide (CO2) laser. The treatment options of skin lesions in patients with SFM are discussed.

Penetration of cotrimoxazole components into skin after a single oral dose. Theoretical versus experimental approach.

Concentrations of trimethoprim and sulfamethoxazole in plasma, cantharidin-induced skin blister fluid and theoretical peripheral compartment were determined in twelve male subjects suffering from bacterial skin diseases after a single oral dose of 0.32 g of trimethoprim and 1.6 g of sulfamethoxazole. Maximum trimethoprim concentrations of 8.5 +/- 1.1 micromol/l in plasma, 5.6 +/- 0.8 micromol/l in blister fluid and 5.8 +/- 2.2 micromol/l in theoretical peripheral compartment were found after 3 +/- 1, 7 +/- 2 and 9 +/- 6 h, respectively. Degree of penetration into blister fluid and theoretical peripheral compartment was 0.94 +/- 0.23 and 1.05 +/- 0.09, respectively. The differences between respective pharmacokinetic parameters of trimethoprim in blister fluid and theoretical peripheral compartment were statistically insignificant. Maximum sulfamethoxazole concentrations of 295 +/- 47 micromol/l in plasma, 182 +/- 46 micromol/l in blister fluid and 239 +/- 58 micromol/l in theoretical peripheral compartment were found after 3 +/- 1, 8 +/- 2 and 7 +/- 4 h, respectively. Degree of penetration into blister fluid and theoretical peripheral compartment was 0.82 +/- 0.20 and 1.04 +/- 0.02, respectively. In contrast to trimethoprim, the differences between respective pharmacokinetic parameters of sulfamethoxazole in blister fluid and theoretical peripheral compartment, except time to maximum concentration, were statistically significant. Cantharidin-induced skin blister fluid method can be used to estimate drug penetration into skin. Due to differences between the respective pharmacokinetic parameters in experimental and theoretical peripheral compartment, in some cases evaluation of drug penetration into skin should not be replaced by the theoretical peripheral compartment calculation.

[Skin penetration of sulfamethoxazole and trimethoprim after oral administration]. / Przenikanie do skóry sulfametoksazolu i trimetoprimu po podaniu doustnym.

The aim of this study was to determine the penetration of trimethoprim, sulphamethoxazole and its main metabolite--N4-acetylsulphamethoxazole into cantharidin-induced skin blister fluid following administration of a single oral combination dose of 320 mg trimethoprim and 1600 mg sulphamethoxazole. Moreover, penetration of the two drugs into skin blister fluid was compared with penetration into the theoretical peripheral compartment calculated on the basis of plasma levels found. The material consisted of 12 male patients with bacterial skin diseases, treated at the Department of Dermatology and Venerology, Pomeranian Academy of Medicine in Szczecin. The age of the patients was 19-64 years (mean 42 +/- 14), weight 61-112 kg (mean 77 +/- 15), height 166-196 cm (mean 175 +/- 8). Prior to enrollment, normal function of gastrointestinal tract, liver and kidneys, and absence of allergy to the drugs studied was ascertained. The susceptibility of pathogens of cotrimoxazole (trimethoprim + sulphamethoxazole) was confirmed with bacteriological tests. Skin blisters were induced by applying 0.25% cantharidin ointment. Drug concentrations in plasma and skin blister fluid were measured with high-performance liquid chromatography. Peak concentrations of trimethoprim in plasma and skin blister fluid were 8.5 +/- 1.1 mumol/L after 3 +/- 1 h and 5.6 +/- 0.8 mumol/L after 7 +/- 2 h, respectively. The differences between both compartments as to parameters measured were statistically significant. In the theoretical peripheral compartment, peak concentration was 5.8 +/- 2.2 mumol/L after 9 +/- 6 h. Half-times of trimethoprim in plasma and skin blister fluid were 11.1 +/- 4.5 h and 12.3 +/- 4.9 h, respectively, and did not differ significantly. The degree of drug penetration into blister fluid defined as the ratio of area under concentration-time curves for blister fluid and plasma was 0.94 +/- 0.23. The differences between pharmacokinetic parameters of trimethoprim in skin blister fluid and theoretical peripheral compartment were not significant. Peak concentrations of sulphamethoxazole in plasma and skin blister fluid were 295 +/- 47 mumol/L after 3 +/- 1 h and 182 +/- 46 mumol/L after 8 +/- 2 h, respectively. The differences between both compartments as to parameters measured were statistically significant. In the theoretical peripheral compartment, peak concentration was 239 +/- 58 mumol/L after 7 +/- 4 h. Half-times of sulphamethoxazole in skin blister fluid and plasma were 9.7 +/- 3.3 h and 10.0 +/- 1.1 h, respectively and did not differ significantly. The drug penetrated into blister fluid to a high extent, although less than trimethoprim, the degree of penetration being 0.82 +/- 0.21. The majority of pharmacokinetic parameters in blister fluid and theoretical peripheral compartment did not differ significantly except for time to peak concentration. Peak concentration of N4-acetylsulphamethoxazole, the main metabolite of sulphamethoxazole, was significantly lower in blister fluid than plasma and took longer to achieve. The half-time of the metabolite was significantly longer in blister fluid than in plasma, whereas the ratio of area under concentration-time curves in these two biological fluids of 0.86 +/- 0.18 was similar to that of the parent drug. The results show that both trimethoprim and sulphamethoxazole administered together penetrate from plasma into skin blister fluid to a great extent and achieve concentrations exceeding the MIC for susceptible pathogens. This finding confirms the usefulness of this treatment in bacterial skin diseases. The cantharidin-induced skin blister is a useful technique to determine the penetration into skin of a drug and its metabolite and to evaluate pharmacokinetic parameters. In some cases, this test cannot be replaced with theoretical calculations based on drug concentrations in blood.