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The administration of flumethasone, by three different routes, its measurement in the plasma and some effects on wool growth in Merino wethers.

Flumethasone was given to Merino wethers weighing 30-50 kg at rates of 0.62-1.35 mg/kg(0.75) by intravenous (experiments 1 and 2), intraruminal (experiment 4) and subcutaneous (experiment 5) routes over 8 days. In experiment 3, 1.2 mg flumethasone/kg(0.75) was given intravenously over 4, 5 or 6 days. The plasma concentration profiles showed concentrations in the order: intravenous greater than subcutaneous greater than intraruminal. Plasma concentration patterns usually were highest during the first 48 h of infusion followed by relatively stable values. This last feature was not evident in experiments when the rate of hormone infusion was increased. Estimates of the metabolic clearance rates for flumethasone in experiments 1, 2 and 5 were 200-700 ml/min during the equilibrium concentration periods. The effects of flumethasone on some aspects of wool growth revealed interactions between the routes of administration, the period of dosage and the rate of wool growth in the recipients. In experiments 1 and 2 intravenous infusion of 1.20-1.33 mg flumethasone/kg(0.75) caused the shedding of all wool fibres about 30 days after treatment. Some effects of dosing sheep with flumethasone at a time when wool growth was decreasing were also observed in experiment 2. Flumethasone given at a rate of 1.2 mg/kg(0.75) over 4, 5 or 6 days caused the shedding of only some wool fibres which were firmly retained on the sheep by the continuous fibres. Intraruminal and subcutaneous infusions of 0.62-1.35 mg flumethasone/kg(0.75) had similar results to the last in the majority of animals although in a few cases no discontinuity of wool fibres was observed. Recovery in wool growth was observed after treatment. Animals regained their pretreatment wool growth in experiments 1, 4 and 5 by 60 days after treatment and probably equalled at that time wool growth in controls. Recovery was retarded in some individuals in experiment 2 and in some groups in experiment 3. In experiment 1, 21 days wool growth was estimated to have been lost. Some aspects of complete versus partial shedding of wool fibres are discussed particularly with reference to wool harvesting. Some similarities in the appearance of fleeces of steroid-treated sheep and naturally shedding animals are also discussed. In some experiments, particularly when the infusion rate of flumethasone was increased (experiment 3), the sheep showed temporary but significant feed refusals during, but more commonly after, treatment. Speculative discussion as to the metabolic causes of this response is included.

Animals

Combination dermatological products: a comparison of betamethasone dipropionate/clotrimazole/gentamicin sulphate and flumethasone pivalate/clioquinol creams.

The combination creams, betamethasone dipropionate/clotrimazole/gentamicin sulphate and flumethasone pivalate/clioquinol, were compared in patients with corticosteroid responsive dermatoses and/or cutaneous fungal and/or bacterial infections. Medication was applied to affected areas twice daily for 28 days. Of 67 patients enrolled, 31 treated with betamethasone/clotrimazole/gentamicin and 33 given flumethasone pivalate/clioquinol were evaluated for efficacy and safety each week during therapy and once 14 days post-therapy. Disease signs and symptoms were less severe in the group given betamethasone/clotrimazole/gentamicin than in the comparative group at days 7 (P = 0.04), 21 (P = 0.02), 28 (P = 0.09), and 42 (P = 0.09) and at patients' last valid visit (P = 0.06). By the last valid visit, signs/symptoms had improved by 82% for patients treated with betamethasone/clotrimazole/gentamicin versus 68% for those treated with flumethasone pivalate/clioquinol. Patients given betamethasone/clotrimazole/gentamicin had statistically significantly better therapeutic responses than those given flumethasone pivalate/clioquinol at day 7 and, by the last valid visit, 19/31 (61%) patients given betamethasone/clotrimazole/gentamicin compared to 15/33 (45%) given flumethasone pivalate/clioquinol had a complete cure or an excellent therapeutic response. Median time of onset of relief of erythema and pruritus was approximately 2 days, regardless of treatment. No adverse reactions were reported.

Administration, Topical

[Effect of salicylic acid on the blanching effect of flumethasone pivalate (author's transl)].

Test results are reported of the effect of salicylic acid on the vasoconstrictive effect of flumethasone pivalate. In specific, the depigmentation of the skin (identical with increase in lightness of the skin) following topical application of flumethasone pivalate was investigated with the aid of an improved spectrophotometric method. Using numeric lightness evaluation it was possible to demonstrate that salicylic acid increases the vasoconstriction.

Adult

Flumethason-induced calving is preceded by a period of myometrial inhibition during luteolysis.

The temporal relationship among changes of the concentrations of the 13,14-dihydro-15-keto metabolite of prostaglandin F2 alpha (PGFM), estrone (E1) and estrone sulphate (E1S) in maternal arterial plasma (MP) and amniotic fluid (AF), the prepartum progesterone (P4) decline in MP, and the evolution of uterine electromyographic (EMG) activity was investigated in 6 cows. Calving was induced by a single i.m. injection of 5 mg flumethason on Day 270 of gestation. The period under investigation was subdivided into four consecutive periods: Period 1 covered the last 2 days before flumethason treatment; Period 2 (mean +/- SEM duration: 16.1 +/- 2.5 h), Period 3 (8.8 +/- 1.1 h), and Period 4 (13.0 +/- 1.5 h) together included the interval between injection and the onset of the expulsive stage of induced parturition. Each was defined by its pattern of uterine EMG activity. During Periods 1 and 2, this activity occurred in long episodes (2-20 min; contractures) at a similar mean (+/- SEM) frequency (0.51 +/- 0.14/h and 0.42 +/- 0.07/h, respectively). No significant differences in hormonal concentrations in MP and AF between these two periods were detected. During Period 3, contractures nearly disappeared (freq: 0.09 +/- 0.05/h), and in MP mean P4 levels were significantly lower and PGFM levels were significantly higher than before. Mean PGFM concentrations in AF were not significantly changed during Period 3. Finally, during Period 4, EMG activity reappeared and a parturient EMG pattern gradually evolved in the presence of a further significant decline of P4 levels and significant increase of PGFM concentrations in MP.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid

Stimulation of androgen and oestrogen concentrations in plasma of cows after administration of a synthetic glucocorticoid (flumethasone) at the end of gestation.

Administration of flumethasone (3.5 mg i.m.) to six cows on day 260 of pregnancy induced parturition in only one animal. In the other five cows circulating concentrations of epitestosterone and conjugated oestrogens increased to reach maximum values (epitestosterone, 13.73 +/- 2.81 nmol/l; conjugated oestrogens, 33.59 +/- 6.87 nmol/l) 2-3 days after treatment. Concentrations of these steroids were raised as long as the synthetic glucocorticoid was present in the circulation (as judged by depression of cortisol concentrations). After clearance of the drug, concentrations of these steroids declined to values present in the control group. Concentrations of unconjugated oestrogens were only slightly raised after flumethasone. In contrast to the effect observed after administration on day 260, treatment on day 270 induced parturition in four of six treated animals. In these cows, mean circulating concentrations of epitestosterone, unconjugated and conjugated oestrogens increased to 9.50 +/- 2.96, 9.62 +/- 1.48 and 36.51 +/- 4.8 nmol/l respectively to reach concentrations observed in the control group at parturition. After parturition the concentrations of epitestosterone and oestrogens declined rapidly in all groups.

Animals

Effect of day gestation on inductions of lambing with flumethasone.

Three-hundred and sixty-nine ewes were examined for the effect of day of flumethasone injection on induction of parturition. Ewes were treated with either 2 mg flumethasone (FLU) or physiological saline (control) on days 138 through 144 of gestation as determined by date of marking by rams. Average time to lambing post-treatment was 86.7 +/- 8.0 hr for FLU-injected ewes and 155.9 +/- 7.9 hr for control ewes (P less than 0.1). Sixty-four percent of the FLU-injected ewes lambed within 72 hr after treatment, compared to 17% of the control ewes (P less than .01). The average interval to lambing for the FLU-treated ewes responding within 72 hr was 49.5 +/- 2.1 hours. FLU treatment on days 140 through 144 of gestation resulted in a shorter (P less than .05) interval from treatment to birth and more (P less than .01) ewes lambing within 72 hr after treatment than did treatment on days 138 and 139.

Animals

[The effectiveness of cholecalciferol and flumethasone for the prevention of hypocalcemic parturient paresis in dairy cows].

Investigations on the efficacy of high doses of cholecalciferol and flumethasone for prophylaxis of hypocalcemic milk fever were performed in dairy cows. Only one cow in the group of 25 treated animals diseased by milk fever, but 5 of 25 control animals showed signs of hypocalcemia. A placenta retention was observed in three treated animals and in four control animals. The results show that the additional application of flumethasone for birth induction after the injection of vitamin D3 was unchanged.

Animals

Flumethasone pivalate (Locorten) in the treatment of oral diseases.

The combination flumethasone pivalate + iodochlorohydroxychinoline drops was used in 40 patients, 24 males and 16 females, mean age 42.6 years, suffering from infectious enanthema (35%), periodontitis (30%), aphthous stomatitis (25%) and abscess due to prosthesis (10%). After application of 2-3 drops of the combination t.i.d. for 2-7 days, satisfactory results were obtained in all the patients. Tolerance was good; mild unwanted effects occurred in 2 patients (5.0%). Thus the combination flumethasone pivalate + iodochlorohydroxychinoline appears to be very effective in the treatment of oral diseases because its action is more rapid and stronger than that of other currently used drugs.

Abscess

[Clinical comparative study of between difluocortolone and flumethasone].

We report the results of a controlled double blind assay of treatment in 51 dermatologic cases, with a new steroid cream (diflucortolone) and an already known one (flumetasone). The diflucortolone valerate was significantly better than the flumetasone pivalate in the treatment of 16 cases of psoriasis, 33 eczemas and two cases of lichên planus.

Clinical Trials as Topic