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PubMedDate not supplied

Bioavailability of clobetasol propionate-quantification of drug concentrations in the stratum corneum by dermatopharmacokinetics using tape stripping.

The concentration of clobetasol propionate in the stratum corneum after application of three different formulations was determined, quantifying the influence of the formulations on the bioavailability of the drug. The stratum corneum was sampled by tape stripping. The concentrations of clobetasol propionate were determined quantitatively by HPLC. After application of Clobetasol Propionate Cream USP, 0.05%, and Temovate Cream, 0.05%, identical amounts of the drug were found in the stratum corneum, whereas after application of Temovate epsilon Emollient, 0.05%, the quantity was clearly decreased. From results obtained measuring the drug concentration in the adjacent sites of the skin where the creams had not been applied, it became clear that clobetasol propionate in Temovate epsilon Emollient, migrated to a large extent in the lateral direction. This explains the lower concentration measured for this formulation in the skin areas where the cream had been applied. In general, a lateral distribution of the applied drug must be taken into account when positioning the application areas on the forearm.

Administration, Cutaneous↗
PubMed1996

0.05% clobetasol 17-propionate cream and ointment but not the corresponding 0.1% triamcinolone acetonide preparations increase skin surface roughness: a possible dissociation of unwanted epidermal and dermal effects.

Repeated open application of clobetasol 17-propionate cream and ointment to normal skin over a period of 6 weeks induced an increase in skin surface roughness as assessed by profilometry (p < 0.05), while 6 weeks' application of triamcinolone acetonide cream and ointment did not. The increase in skin roughness with clobetasol 17-propionate cream turned out to be greater than with ointment containing identical amounts of clobetasol 17-propionate (p < 0.05). A clear-cut correlation between increase of skin surface roughness and skin thickness as assessed by high-frequency ultrasound could be demonstrated only with clobetasol 17-propionate cream and ointment.

Administration, Topical↗
PubMed1987

Adrenal suppression following low-dose topical clobetasol propionate.

The use of topical steroids is associated with adverse systemic effects such as suppression of the hypothalamic-pituitary-adrenal (HPA) axis, and application of more than 50 g per week of clobetasol propionate cream has been shown to cause secondary adrenal failure. We describe 4 patients who used clobetasol propionate cream over a prolonged period; 3 patients used less than 50 g per week (7.5, 25 and 30 g per week) and yet all developed secondary adrenal failure for up to 4 months after cessation of therapy. Adrenal insufficiency following prolonged use of clobetasol propionate in moderate dosages may therefore be more common than previously recognized. It is suggested that the metyrapone test, which conveniently examines the entire HPA axis, should be employed in patients receiving long-term topical clobetasol propionate cream and that glucocorticoid supplementation should be given during episodes of stress, such as infections and surgery, for up to 4 months after cessation of therapy.

Administration, Topical↗
PubMed1998

Pituitary-adrenal suppression in preterm, very low birth weight infants after inhaled fluticasone propionate treatment.

Systemic corticosteroids prescribed for treatment of pulmonary diseases in preterm, very low birth weight infants caused severe suppression of the hypothalamic-pituitary-adrenal axis and produced serious physiological and metabolic disturbances. However, the effect of inhaled corticosteroids on their pituitary-adrenal functions is not known. We prospectively evaluate the pituitary-adrenal function using the human CRH stimulation test in a cohort of very low birth weight infants at risk for hypothalamic-pituitary-adrenal axis suppression in a double blind, randomized pilot study designed for assessing the efficacy and adverse effects of inhaled fluticasone propionate in newborn preterm infants who required mechanical ventilation for treatment of respiratory distress syndrome. Twenty-five preterm (< 32 gestational weeks), very low birth weight (< 1500 g) infants were randomized to receive inhaled fluticasone propionate (n = 13) or a placebo inhaler (n = 12). The medication was given every 12 h (fluticasone propionate, 1,000 micrograms/day) for 14 days. All surviving infants had their pituitary-adrenal functions assessed by human CRH test on the following morning immediately after completion of the 2-week course. All basal (0 min) and post-stimulation (15, 30, and 60 min) plasma ACTH and serum cortisol concentrations were significantly suppressed in the inhaled fluticasone group compared to their corresponding levels in the placebo group [basal plasma ACTH concentrations (F = 6.0; P = 0.02), poststimulation plasma ACTH concentrations (F > 8.6; P < 0.01), basal serum cortisol concentrations (F = 5.6; P = 0.03), and poststimulation serum cortisol concentrations (F > 15.6; P < 0.001)]. This is the first study in very low birth weight infants that demonstrates unequivocally that cumulative high dose inhaled corticosteroids can induce moderately severe suppression of both the pituitary and adrenal glands. The systemic bioactivity is probably associated with pulmonary vascular absorption, which effectively circumvents the hepatic first pass metabolism. Until the question of safety can be adequately addressed, inhaled fluticasone propionate should be used with cautionin preterm infants.

Administration, Inhalation↗
PubMed1988

Effects of 2-(3-methyl-cinnamyl-hydrazono)-propionate on fatty acid and glucose oxidation in the isolated rat diaphragm using 14C-labelled substrates. Hydrazonopropionic acids, a new class of hypoglycaemic substances, VIII.

The influence of 2-(3-methyl-cinnamyl-hydrazono)-propionate on the utilization of various substrates in isolated rat hemidiaphragms was investigated in comparison with other hypoglycaemic compounds. The effect of 2-(3-methyl-cinnamyl-hydrazono)-propionate was concentration-dependent. At a concentration of 0.5 mmol/l 2-(3-methyl-cinnamyl-hydrazono)-propionate, glucose utilization increased from 0.276 +/- 0.043 mumol.g-1.l-1 to 0.894 +/- 0.303 mumol.g-1.l-1 (p less than 0.05). Pyruvate and lactate utilization were stimulated to a lesser extent, while acetate utilization remained nearly constant. At a concentration of 2 mmol/l 2-(3-methyl-cinnamyl-hydrazono)-propionate, the oxidation of palmitate decreased from 0.214 +/- 0.017 mumol.g-1.l-1 to 0.060 +/- 0.005 mumol.g-1.l-1, while the oxidation of octanoate was not decreased. These findings point to a stimulation of the glycolytic flux by inhibition of long-chain fatty acid oxidation.

Animals↗
PubMed2004

Effect of fluticasone propionate nasal spray on bioavailability of intranasal hydromorphone hydrochloride in patients with allergic rhinitis.

STUDY OBJECTIVE: To investigate the effect of the nasal corticosteroid fluticasone propionate on the bioavailability and pharmacokinetics of single-dose intranasal hydromorphone hydrochloride in patients with allergic rhinitis. DESIGN: Randomized, three-way, crossover pharmacokinetic study. SETTING: University clinical research unit. PATIENTS: Twelve patients with allergic rhinitis. INTERVENTION: Hydromorphone hydrochloride 2.0 mg was administered by intravenous infusion (treatment A), intranasal spray without allergic rhinitis treatment (treatment B), and intranasal spray after 6 days of fluticasone propionate (treatment C). Blood samples were collected serially from 0-16 hours. MEASUREMENTS AND MAIN RESULTS: Pharmacokinetic parameters were determined by noncompartmental methods. An analysis of variance (ANOVA) model was used for statistical analysis. Mean (% coefficient of variation) absolute bioavailability of intranasal hydromorphone was 51.9% (28.2) and 46.9% (30.3) in patients with allergic rhinitis with and without treatment with fluticasone propionate, respectively. Mean maximum concentration (Cmax) values were 3.02 and 3.56 ng/ml, respectively. No statistical differences in Cmax and area under the concentration versus time curve were detected between intranasal treatments. Bioavailability values for both intranasal treatments were lower than those in healthy volunteers (57%). Median time to Cmax (Tmax) values were significantly different (p=0.02) for treatments B and C (15 and 30 min, respectively) using rank-transformed Tmax for ANOVA. Adverse effects were consistent with known effects of hydromorphone administered by other routes, with the exception of bad taste after intranasal administration. CONCLUSION: Hydromorphone was rapidly absorbed after nasal administration, with maximum concentrations occurring for most subjects within 30 minutes. Allergic rhinitis may affect pain management strategies for intranasal hydromorphone, with a delay in onset of action for patients treated with fluticasone propionate.

Administration, Intranasal↗
PubMed1995

Efficacy of laidlomycin propionate to reduce ruminal acidosis in cattle.

Three trials were conducted to evaluate the efficacy of laidlomycin propionate (LP) to reduce the incidence and severity of ruminal acidosis in cattle fed high-grain finishing diets. In each trial, LP was fed at 0, 6, or 12 mg/kg of diet DM. In two acidosis-challenge trials, ruminally fistulated steers were fed (DM basis) a 50% concentrate diet and then fed a 95% concentrate diet at a specific intake (2.75% BW) or steers were dosed intraruminally with a 100% concentrate diet. Laidlomycin propionate did not alter ruminal pH or total acid concentrations, but in Trial 1 the 6 mg/kg level altered (P < .10) the molar proportions of the acids, increasing total ruminal VFA and decreasing ruminal lactate. In Trial 3, a finishing trial, LP reduced (P < .10) intake day-to-day variation of individually fed steers during a 13-d adaptation period from a 65 to a 100% concentrate diet, suggesting reduced incidence of subacute acidosis. Feed intake was lower (P < .05) during the first 13 d of the trial due to LP but was not affected over the entire trial. Laidlomycin propionate improved feed efficiency (gain/feed) when calculated on a live weight basis (linear, P = .05) or carcass weight basis (linear, P = .20). Laidlomycin propionate does not prevent ruminal acidosis, but it may reduce the severity of ruminal acidosis during adaptation to a 100% concentrate diet.

Acidosis↗
PubMed2001

A randomized, double-blind, multicenter trial comparing fluticasone propionate cream, 0.05%, and hydrocortisone-17-butyrate cream, 0.1%, applied twice daily for 4 weeks in the treatment of psoriasis.

The efficacy, safety, and tolerability of twice-daily fluticasone propionate (Cutivate) cream, 0.05%, and hydrocortisone-17-butyrate cream, 0.1%, were compared in 125 patients with moderate-to-severe psoriasis in a 4-week, multicenter, double-blind, randomized, active-control study. Clinical assessments of response to therapy, made at weekly intervals, included physicians' gross assessment of clinical response, improvement in signs and symptoms, and patients' assessment of treatment effects. Based on physicians' gross assessment, fluticasone propionate cream was superior to hydrocortisone-17-butyrate cream at day 22 (after 3 weeks' treatment) and at the end-of-treatment visit (P < .05). Cleared, excellent, or good end-of-treatment response rates were 50/63 (79%) for fluticasone propionate compared with 41/60 (68%) for hydrocortisone-17-butyrate. Adverse events were limited to mild-to-moderate pruritus with fluticasone propionate (3.2%) and hydrocortisone-17-butyrate (1.7%) and mild skin warmth with hydrocortisone-17-butyrate (1.7%).

Administration, Topical↗
PubMedDate not supplied

The effects of fluticasone propionate on nasal epithelial potential difference.

BACKGROUND: Human airway epithelium maintains homeostasis of the fluid and salt composition at the airway surface by a regulated transport of sodium and chloride ions. The volume and composition of airway surface liquid have been shown to be important in the pathogenesis of cystic fibrosis, nasal inflammatory disease, and nasal polyposis. The presence of functional epithelial sodium and chloride channels in the airway epithelium can be evaluated electrically by measuring the voltage across the nasal epithelium (Vt). Because fluticasone propionate is commonly used to treat nasal inflammatory diseases, we tested its effect on the nasal ion transport. METHODS: A single-blind prospective trial was performed on 12 healthy volunteers. Subjects were randomized to receive either fluticasone propionate or normal saline nasal spray twice daily for 2 weeks. We measured the nasal voltage at baseline, days 3 and 14, and 2 weeks after cessation of treatment. The basal voltage, the change in voltage after perfusion with amiloride (sodium channel blocker), and the change in voltage after perfusion with isoproterenol in a low-chloride buffer (chloride channel activator) were recorded. Saccharin clearance times were measured also. RESULTS: Two-week treatment with fluticasone propionate resulted in a significant increase in the change in Vt after perfusion with amiloride. There was no significant change in the group treated with normal saline. These findings also were observed on day 3 and were reversed completely after the 2-week washout period The increase in amiloride-sensitive Vt did not result in a decrease in mucociliary clearance. CONCLUSIONS: This study suggests that one effect of fluticasone propionate use on nasal mucosa in normal volunteers is increased epithelial sodium absorption.

Administration, Intranasal↗
PubMed2006

Clobetasol propionate for psoriasis: are ointments really more potent?

BACKGROUND: Clobetasol propionate is the most common topical therapy used for psoriasis in the US. Conventional dermatologic wisdom is that ointment preparations provide the highest potency (due to their occlusive nature and moisturizing ability) and are best suited for psoriasis. However, patients often find application of ointment to be messy, raising concerns about both short-term and long-term adherence to treatment. This article reviews the current literature and assesses the relative potency of clobetasol propionate ointment compared to other clobetasol propionate preparations in the treatment of psoriasis. Relevant literature was identified by PubMed and Google searches. We included studies of psoriasis that reported the percentage of subjects that achieved desired efficacy endpoints, as well as studies that reported the subjects' mean change in symptoms from baseline. We excluded studies conducted before 1980 and those that allowed concomitant treatments. OBSERVATIONS: Efficacy rates ranged from 17% to 80% for the different vehicles: ointment, solution, foam, cream, lotion, shampoo, and emollient. CONCLUSIONS: Clobetasol propionate is a very effective treatment for psoriasis. Ointment preparations have similar efficacy to other preparations in clinical trial situations. In clinical practice, a situation in which patient preferences are more likely to affect compliance, it may be best to choose whichever vehicle patients find preferable.

Administration, Topical↗
PubMed1991

Dose tolerance study of fluticasone propionate aqueous nasal spray in patients with seasonal allergic rhinitis.

A multicenter, double-blind, parallel-group, dose-tolerance study was conducted to evaluate the safety of fluticasone propionate aqueous nasal spray, a potent new corticosteroid preparation. Ninety-seven adult patients with moderate to severe seasonal allergic rhinitis during the fall weed season received either placebo or fluticasone propionate in doses of 50, 200, or 800 micrograms twice daily for 4 weeks. Safety evaluations included adrenal function evaluation by morning plasma cortisol concentration, response to ACTH stimulation, and 24-hour urinary free cortisol excretion. There was no evidence of effects on adrenal function at any dose. The severity, nature, and frequency of adverse events were similar across all treatment groups, including placebo. Drug-related adverse events were consistent with local nasal irritation. The groups receiving fluticasone propionate showed greater improvement in nasal symptoms (obstruction, rhinorrhea, sneezing, and itching) than did the placebo group. The results demonstrate that fluticasone propionate aqueous nasal spray is safe in doses up to 1600 micrograms per day and effective in the treatment of seasonal allergic rhinitis.

Administration, Intranasal↗
PubMed1982

Steroid levels after intramuscular injection of testosterone propionate in the caprine.

Nine sexually mature intact grade does were injected intramuscularly with testosterone propionate and subsequent plasma steroid concentrations determined and male-like behavior recorded. The does received either 100 mg testosterone propionate every three days for six treatments, total dose 600 mg (N = 5); 50 mg testosterone propionate daily for eighteen days, total dose 900 mg (N = 2) or 10 mg testosterone propionate daily for eighteen days, total dose 180 mg (N = 2). The treatments induced male-like sex behavior, the intensity of which was related to the dose of exogenous testosterone used, the regimen of administration, and the plasma levels of testosterone. Exogenous testosterone treatment had minimal effect on the subsequent reproductive activity of the does.

Animals↗
PubMed1995

A comparison of budesonide nasal dry powder with fluticasone propionate aqueous nasal spray in patients with perennial allergic rhinitis.

There is circumstantial evidence that the incidence of allergic rhinitis is becoming increasingly common. There may also be a need for more potent drugs with minimal local and systemic side effects. This study has compared the efficacy and safety of budesonide delivered as nasal dry powder with fluticasone propionate aqueous nasal spray in the treatment of perennial allergic rhinitis. Ninety-eight patients participated in a randomized, parallel group and partly blinded study. Treatment consisted of budesonide dry powder (Rhinocort Turbuhaler) at once daily doses of 200 micrograms (n = 24) or 400 micrograms (n = 22), fluticasone propionate (200 micrograms) once daily (n = 25), and placebo for budesonide dry powder (n = 27). A six-week treatment period was preceded by a two-week baseline period without treatment. Efficacy was assessed by daily subjective scoring of nasal symptoms. Safety was assessed by rhinoscopy, analysis of urine cortisol, and questioning of adverse events. All active treatments were significantly superior to placebo in controlling nasal symptoms. No significant differences in efficacy were found between the two budesonide regimens and fluticasone propionate. Adverse events were few and minor, and non-significantly distributed between treatments. In conclusion, this study shows that budesonide dry powder administered from Turbuhaler (200 or 400 micrograms) and fluticasone propionate aqueous spray (200 micrograms) administered in once daily doses, are effective and safe treatments of perennial allergic rhinitis. These novel treatments may enhance the current available alternatives in clinical practice.

Administration, Topical↗
PubMed1994

[The Testosterone Propionate Reference Standard (Control 881) of the National Institute of Health Sciences].

Raw testosterone propionate material was tested for preparation of the "Testosterone Propionate Reference Standard (Control 881)". Analytical data obtained were as follows: loss on drying, 0.1%; melting point, 120.6 degrees C; optical rotation [alpha]20D = + 85.4 degrees; ultraviolet spectrum, lambdamax = 241 nm and specific absorbance E 1cm1% (241 nm) = 483; infrared spectrum, the same as that of the NIHS Testosterone Propionate Reference Standard; thin-layer chromatography, no impurities were detected; high-performance liquid chromatography (HPLC), one impurity was detected; assay result, 100.6% by UV spectrophotometry. Based on the above findings, the raw material was authorized as the Testosterone Propionate Reference Standard (Control 881) of the National Institute of Health Sciences.

Chemical Phenomena↗
PubMed1996

Topical clobetasol propionate compared with placebo in the treatment of unretractable foreskin.

OBJECTIVE: To assess whether it is the steroid alone or the gentle physical retraction combined with ointment that is responsible for the excellent results observed with topical steroid treatment of unretractable foreskin. DESIGN: Prospective, randomised, double-blind study. SETTING: University hospital, Sweden. SUBJECTS: 30 Boys randomised to be treated with clobetasol propionate (n = 15) or placebo (n = 15). INTERVENTIONS: The boys were examined 1, 2 and 6 months, respectively, after treatment. MAIN OUTCOME MEASURES: Comparison between the effects of clobetasol propionate and placebo. RESULTS: Two patients in the steroid group and one in the placebo group withdrew from the study. 10 Boys in the steroid group showed an improvement within 2 months. The remaining 3 boys had no effect and were circumcised. Histopathological examination showed lichen sclerosus et atrophicus. Seven boys in the placebo group improved. The 7 non-responders were prescribed clobetasol propionate ointment, and all 7 improved. CONCLUSION: 17 of 27 boys referred with "phimosis" were successfully treated with an ointment and gentle traction. When clobetasol propionate was given the non-responders success rate was increased to 24/27 (89%).

Administration, Topical↗
PubMed2026

Phylum-wide propionate degradation and its potential connection to poly-gamma-glutamate biosynthesis in Candidatus Cloacimonadota phylum.

The candidate phylum Cloacimonadota is frequently detected in anoxic environments such as anaerobic digestion (AD) reactors, hydrothermal vents, and deep-sea sediments, yet its metabolism remains poorly understood. Metagenomic evidence suggests capacities for amino acid fermentation, carbohydrate degradation, as well as a potential role in syntrophic propionate oxidation (SPO), a key bottleneck in AD. However, a complete methylmalonyl-CoA (mmc) pathway, central to SPO, has not been previously identified in Cloacimonadota genomes. Here, we report results from an acidified lab-scale anaerobic baffled reactor fed with sugar beet pulp, where an increase in the relative abundance of Cloacimonadota correlated with recovery of methanogenesis, resulting in increased methane content in the produced biogas. Metagenomic and metatranscriptomic analyses enabled metabolic reconstruction of the dominant Cloacimonadota operational taxonomic unit (OTU). Furthermore, using a curated database of 204 genome-resolved Cloacimonadota species, we characterized the phylum-level metabolic potential. Comparative genomics revealed alternative proteins, including 2-oxoglutarate:ferredoxin oxidoreductase and aspartate aminotransferase, likely to substitute for missing enzymes in the classical mmc pathway. These proteins were widely distributed and highly conserved across the analyzed Cloacimonadota genomes, suggesting that this variant of the SPO pathway could represent a phylum-specific trait. Moreover, we hypothesize that these alternative pathway steps may link propionate metabolism to protein degradation and poly-&#x3b3;-glutamate biosynthesis. Network analysis identified the methanogenic archaeon Methanothrix as a potential syntrophic partner, an interaction further supported by propionate-fed enrichment cultures showing co-occurrence of Cloacimonadota and Methanothrix species. Our study sheds light on the Cloacimonadota metabolism, advancing our understanding of their ecological roles and potential for biotechnological applications.

Propionates↗
PubMed1963

Succinic acid turnover and propionate production in the bovine rumen.

High velocity constants for conversion of added succinate to propionate, together with estimations of pool size, showed that extracellular succinate is the major precursor of the propionate formed in the rumen. Some bacteria give off succinate as a final fermentation product which is decarboxylated by others to propionate.

Animals↗
PubMed1963

CONVERSION OF GLUCOSE-C14 TO PROPIONATE BY THE RUMEN MICROBIOTA.

Baldwin, R. L. (Michigan State University, East Lansing), W. A. Wood, and R. S. Emery. Conversion of glucose-C(14) to propionate by the rumen microbiota. J. Bacteriol 85:1346-1349. 1963.-Rumen microbiota enriched on three different diets calculated to present different levels of available carbohydrate were incubated with glucose-1-C(14), glucose-2-C(14), and glucose-6-C(14) to determine the contribution of the randomizing (succinate) and nonrandomizing (acrylate) routes to propionate. The propionate was labeled as though 70 to 100% was formed via the randomizing route and 0 to 30% via the nonrandomizing route. The contribution of the acrylate pathway increased with higher carbohydrate availability of the diet. These results are discussed with respect to earlier data using lactate-2-C(14) and lactate-3-C(14), and a unifying concept for both sets of data is presented.

Acrylates↗