Synalar
Effects of fluocinolone acetonide on mouse skin sterol metabolism and two-stage carcinogenesis.

Fukao K, Tanimoto Y, Kayata Y, Yoshiga K, Takada K, Okuda K.

Department of Oral and Maxillofacial Surgery, Hiroshima University, School of Dentistry, Japan.

Fluocinolone acetonide (FA) is one of the most potent synthetic glucocorticoids and is known to possess an anti-tumor promoting activity. An attempt was made to evaluate this activity by estimating tumor promoting activity. Unexpectedly, when 10 micrograms of FA was applied alone or after a single application of a subcarcinogenic dose of 3-methylcholanthrene to mouse skin, results suggested that FA itself may be a tumor promoter or a complete carcinogen. Other glucocorticoids tested, e.g. dexamethasone, hydrocortisone and prednisolone, also revealed similar effects but were less potent than FA. To verify the possibility that glucocorticoid is a complete carcinogen or a tumor promoter, a tumor incidence experiment was performed for 24 weeks. As a result it was found that FA possesses a tumor promoting activity at some dose levels but no tumor initiating activity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3409469&dopt=Abstract fluocinolone Synalar



Synalar
Temperature and pH dependence of fluocinolone acetonide degradation in a topical cream formulation.

Kenley RA, Lee MO, Sukumar L, Powell MF.

Syntex Research, Palo Alto, California 94304.

We investigated the degradation of fluocinolone acetonide (FA) incorporated into an oil-in-water cream base. The study examined the influence of temperature (23 to 80 degrees C) and cream pH (pH 2.3 to 6) on FA degradation rates. FA degradation followed pseudo-first-order kinetics and adhered to the Arrhenius expression over the entire temperature range investigated. At all temperatures, the pH strongly influenced the observed degradation rate constant (kobs) values, with rate minima observed near pH 4. The FA log(degradation rate)-pH profiles were consistent with a reaction mechanism requiring drug hydrolysis catalyzed by hydroxide and hydrogen ions. Taking into account both the temperature and the pH dependence of FA degradation permits calculating kobs values from the following equation: kobs = exp[22.5 - (17,200/RT)] + exp[38.7 - (22,200/RT)] x [H+] + exp[49.5 - (21,100/RT)] x [OH-] where the three bracketed terms represent Arrhenius expressions for neutral, acid-catalyzed, and base-catalyzed hydrolysis reactions. FA degradation in the cream base parallels the degradation of a related steroid (triamcinolone acetonide) in an aqueous alcohol solution. The equivalence between FA and triamcinolone acetonide kinetics in the different reaction media suggests that in the cream base, FA degradation is limited to an aqueous phase largely unperturbed by the presence of nonaqueous constituents that comprise the cream formulation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3508541&dopt=Abstract fluocinolone Synalar



Synalar
Teratogenicity study of the new glucocorticosteroid budesonide in rabbits.

Kihlstrom I, Lundberg C.

16 alpha,17 alpha-Butylidenedioxy-11 beta,21-dihydroxy-pregna-1,4-diene-3,20-dione (budesonide), a newly developed glucocorticosteroid, was administered subcutaneously to pregnant rabbits at doses of 0.01, 0.06 and 0.29 mumol/kg during the organogenetic period. As a reference compound the glucocorticosteroid fluocinolone acetonide, at the dose 0.28 mumol/kg, was used. In the group given 0.06 mumol/kg 2 dams out of 15 aborted. All animals receiving 0.29 mumol/kg aborted. All dams receiving fluocinolone acetonide aborted. The food consumption was reduced in all groups given budesonide. The body weight change was dose-dependently reduced for the groups receiving budesonide. The group receiving fluocinolone acetonide also showed a negative body weight change compared with the control group. The affected litter parameters were: reduced litter and fetal weight in the groups receiving 0.01 and 0.06 mumol/kg of budesonide, indicating intrauterine growth retardation. Furthermore, the frequency of fetal abnormalities, mainly skeletal anomalies, was significantly increased in the group receiving 0.06 mumol/kg of budesonide. The anomalies seen were mostly different kinds of delayed development of the bones in the skull and at the vertebra. A direct teratogenic effect cannot be excluded but severe maternal toxic reactions may have contributed to the pregnancy outcome.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3566856&dopt=Abstract fluocinolone Synalar



Synalar
Evaluation of efficacy and tolerability of K-FA fluocinolone acetonide tape.

Cattaneo M, Betti R, Lodi A, Beretta A.

In order to assess the efficacy and tolerability of a fluocinolone acetonide tape (8 micrograms/cm2), 30 volunteer out-patients, 11 females and 19 males, mean age 43.4 years, affected by different kinds of dermatoses were treated. The tape was applied once or twice daily for an average period of 9.3 days. At the beginning and the end of the treatment, detailed dermatological and blood chemistry examinations were performed in all the patients. The clinical results were excellent for all the dermatoses treated. Itching at the site of application was reported by two patients and slight atrophy was observed in one patient. The patients' compliance was excellent. The blood chemistry tests showed no significant variation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3596870&dopt=Abstract fluocinolone Synalar