temarotene and Acne-Vulgaris

1,2,3,4-Tetrahydro-1,1,4,4-tetramethyl-y-[(E)-alpha-methylstyryl]- naphthalene (Ro 15-0778), a potent inhibitor of sebaceous gland activity in several animal models has been administered to male volunteers in dosages of 1, 2, 3, and 6 mg/kg/day and 2 g/day for 8 weeks. Sebum production was measured before treatment and after 4 and 8 weeks of therapy. At the dosage levels of 1, 2, 3, and 6 mg/kg/day there was no decrease in sebum secretion. With the dosage of 2 g/day, a significant decrease in sebum secretion was seen after 8 weeks of treatment with Ro 15-0778.

Topics: Acne Vulgaris; Administration, Oral; Depression, Chemical; Humans; Male; Retinoids; Sebaceous Glands; Sebum; Secretory Rate

A new approach studying the characteristics of the stratum corneum is presented: the electrophoretic mobility of corneocytes by laser Doppler spectroscopy. The detergent scrub technique was used for harvesting corneocytes from three body regions (forehead, palm, and sole) of normal persons (n = 20) under casual conditions and after thorough defattening of the skin with 70% isopropyl alcohol or petrol. Similarly, cells from the forehead, shoulder, and palm were obtained from 22 acne patients treated with isotretinoin (13-cis retinoic acid) 0.5-0.7 mg/kg body weight (b.wt.)/day for 12-16 weeks, and in patients receiving arotinoid (Ro 15-0778) 192 mg (n = 5) or 500 mg (n = 5) per kg/b.wt./day for 6 weeks (forehead and shoulder). In another experiment, cell suspensions with a pH ranging from 5.0-7.3 were evaluated. Measurements were performed by dynamic laser light scattering. This laser application allows exact electrophoretic mobility measurements in a short time (3 min). When cells pass the laser beam, the scattered light is frequency-shifted due to the optical Doppler effect. These frequency shifts are analyzed by the heterodyne light beating technique. The analog signal of the photodetector is converted into a power spectrum by Fourier analysis. This power spectrum represents the spectrum of electrophoretic cell mobility distribution. Results showed different electrophoretic mobility values for corneocytes dependent on the topographic region: forehead 1.18 +/- 0.16, palm 1.10 +/- 0.14, and sole 0.83 +/- 0.10 (means +/- SEM) micron cm/Vs. Defattening with isopropyl alcohol decreased the mobility values to 0.90 +/- 0.09 (p less than or equal to 0.01), 0.95 +/- 0.10, and 0.77 +/- 0.10 micron cm/Vs respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acne Vulgaris; Adolescent; Adult; Epidermis; Female; Humans; Isotretinoin; Male; Retinoids; Rheology; Sebaceous Glands; Tetrahydronaphthalenes; Tretinoin

A rapid, sensitive and selective high-performance liquid chromatographic (HPLC) assay was developed for the determination of (E)-1,2,3,4-tetrahydro-1,1,4,4-tetramethyl-6-(1-methyl-2- phenylethenyl)naphthalene (I) and its phenolic metabolite, (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-2- methylethenyl]phenol (II) in plasma. The assay for both compounds involves precipitation of the plasma proteins with acetonitrile, followed by extraction of the entire mixture into methyl tert.-butyl ether and subsequent analysis by reversed-phase HPLC. The overall recovery of I and II was 96.9 +/- 5.3 and 96.2 +/- 5.8% for dog plasma, 80.0 +/- 4.0 and 93.5 +/- 5.0% for human plasma and 97.4 +/- 2.9 and 97.6 +/- 9.6% for rat plasma, respectively. The sensitivity limit is 20 ng/ml of plasma for both compounds I and II using UV detection at 280 nm. The HPLC assay was used in studies in the dog and in the rat.

Topics: Acne Vulgaris; Animals; Anti-Infective Agents, Local; Biotransformation; Chromatography, High Pressure Liquid; Dogs; Drug Stability; Female; Humans; Indicators and Reagents; Male; Naphthalenes; Rats; Retinoids; Sex Factors; Species Specificity; Spectrophotometry, Ultraviolet; Temperature; Tetrahydronaphthalenes