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At least 19 recordsLinked to original sources

Comparative teratogenicity of triamcinolone acetonide, triamcinolone, and cortisol in the rat.

Pregnant rats were injected im with 0.5 mg/kg triamcinolone acetonide (TAC) on day 12, 13, or 14 of gestation and the fetuses were examined for cleft palate on day 20. All three TAC-treated groups showed an increased proportion of fetuses with cleft palate compared to an untreated control group. Only the group treated on day 13 showed a significant increase in the proportion of litters affected. This indicates that day 13 of gestation is the most sensitive day for cleft palate induction by TAC in the rat. Pregnant rats were then treated on day 13 of gestation with either TAC, triamcinolone (TA), or cortisol. TAC was 59 times as potent as TA in inducing cleft palate, with ED50 values of 1.1 mg/kg and 65 mg/kg respectively. Cortisol induced a significant increase in cleft palates at 500 mg/kg, but the efficacy of this compound was too low to calculate an ED50 and relative teratogenic potency value. Other developmental abnormalities including umbilical hernias, resorption, and fetal death resulted from TAC treatment. Fetal growth retardation was produced by all three compounds. The rank order of teratogenic potency was determined to be TAC greater than TA greater than cortisol.

Animals↗

Histopathological findings of cleft palate in rat embryos induced by triamcinolone acetonide.

Triamcinolone acetonide (TAC), a synthetic glucocorticoid, induces cleft palate resulting from poor development of palatal shelves in mice. However, TAC has no effect on medial edge epithelial cells (MEE cells) in secondary palatal shelves. In the present study, we examined the relationship between the pathogenesis of cleft palate and the effects on MEE cells and palatal mesenchymal cells in rat embryos/fetuses exposed to TAC. Pregnant Wistar Hannover rats were given TAC intramuscularly at 0.5 mg/kg at gestation days (Day) 12, 13, and 14, then embryos/fetuses were harvested on Days 14.5, 15, 16 and 20. The effects of TAC were as follows; an inhibition of palatal mesenchymal cell proliferation on Day 14.5, a decrease in the density of palatal mesenchymal cells and MEE cells, and expression of epidermal growth factor (EGF) receptors in MEE cells on Day 15, and stratified squamous differentiation of MEE cells with expression of cytokeratin and EGF receptors on Day 16. These findings indicated that TAC inhibited the proliferation of mesenchymal cells and affected the differentiation of MEE cells into stratified squamous epithelia in the palatal shelves of rat embryos. However, these stratified squamous MEE cells partially fused with each other. Thus, we suspected that a major contributing factor to the formation of TAC-induced cleft palate might not be the altered differentiation of MEE cells, but the inhibition of mesenchymal cell proliferation.

Animals↗

Relative efficacy of fluocinolone acetonide compared with triamcinolone acetonide in treatment of oral lichen planus.

Twenty patients with oral lichen planus and topically treated with fluocinolone acetonide in orabase 0.1% (FAO) were compared with 20 treated with triamcinolone acetonide in orabase 0.1% (TAO). During 4 wk of treatment the lesions in 13 of 19 patients could be effectively cured with FAO whereas only 8 of 19 patients were cured with TAO. These differences were statistically significant. There were no differences in blood pressure, plasma cortisol or number of circulating lymphocytes after treatment with FAO, but the number of eosinophils was reduced in every case after treatment for 6 months. There was no permanent adrenal cortical suppression after treatment for 6 months. Acute pseudomembranous candidiasis during the treatment was common but could be cured with antifungal drug in every case. This study shows that FAO in a majority of cases is an effective treatment of oral lichen planus without any serious clinical side effects apart from treatable candidiasis.

Administration, Oral↗

Submacular deposition of triamcinolone acetonide after triamcinolone-assisted vitrectomy.

PURPOSE: We describe a case demonstrating a submacular deposition of triamcinolone acetonide (TA) after a TA-assisted vitrectomy for retinal detachment. DESIGN: Interventional case report. METHODS: A 48-year-old Japanese man with rhegmatogenous retinal detachment in his left eye underwent a TA-assisted vitrectomy, endolaser photocoagulation, and sulfur hexafluoride (SF(6)) gas tamponade. RESULTS: At the end of the surgery and the day after undergoing vitrectomy, the deposition of TA was observed between the retinal pigment epithelium and neurosensory retina in the submacular area. These TA granules disappeared after 2 weeks. Two months after the operation, the retina was observed to be successfully attached and no abnormality was observed in the macula. The patient's visual acuity improved to 20/16, and no ophthalmoscopic or functional damage was observed. CONCLUSION: No apparent adverse effect was found in this case demonstrating a submacular deposition of TA.

Fluorescein Angiography↗

Treatment of asthma in children with triamcinolone acetonide aerosol.

Triamcinolone acetonide aerosol, 100 microgram qid, was administered for 8 wk to 5 steroid-dependent asthmatic children and 10 who had not previously required continual corticosteroid treatment. Symptomatic control and pulmonary function improved in all 15 children despite discontinuation of oral corticosteroids in 3 of the steroid-dependent children. Determination of morning plasma cortisol concentrations disclosed no evidence of substantial adrenal suppression. Satisfactory symptomatic control has subsequently been maintained for 6 to 32 mo with doses of 100 microgram bid to 300 microgram qid without more extreme changes in plasma cortisol concentrations than were observed during the first 8 wk.

Adolescent↗

Pars plana vitrectomy with removal of posterior hyaloid face in treatment of refractory diabetic macular edema resistant to triamcinolone acetonide.

BACKGROUND: Triamcinolone acetonide (TA) has recently been used to treat diabetic macular edema (DME) but its effectiveness is limited. CASES: Three patients (three eyes) with unresolved diffuse DME who did not respond to a posterior sub-Tenon's injection of TA underwent vitrectomy. OBSERVATIONS: Intraoperatively, it was found that all of the eyes had a posterior hyaloid face that was adherent to a large area of the posterior pole retina, although this had not been detected by slit-lamp biomicroscopy or optical coherence tomography. After vitrectomy and removal of the posterior hyaloid face, there was a significant reduction in the central macular thickness of all three eyes and an improvement in the visual acuity of the patients. CONCLUSIONS: When TA treatment is not effective for DME, vitrectomy with the complete removal of the posterior hyaloid face, including removal of the internal limiting membrane, should be considered.

Aged↗

Pulmonary distribution and kinetics of inhaled [11C]triamcinolone acetonide.

UNLABELLED: Triamcinolone acetonide (TAA) is an anti-inflammatory steroid used for topical treatment of allergic rhinitis and asthma. Drug deposition onto target tissues is an important parameter, so methods for accurate deposition measurement are needed. Lung deposition is especially problematic to measure because of the large field of view and low relative drug penetration. Our main objective was to use PET to measure the deposition and postdeposition kinetics of TAA in the lung after administration from the Azmacort inhaler. The second objective was to evaluate changes in distribution caused by the inhalation spacer that is built into the product. METHODS: 11C-labeled TAA was formulated as the Azmacort product, 5 healthy volunteers inhaled it, and PET scans were obtained of its distribution in the head and chest. Region-of-interest analysis with CT overlay was used to analyze the distribution and kinetics in the airway and lung. RESULTS: From 10% to 15% of the inhaled drug dose was deposited in target airway regions in a distally decreasing pattern. Deposition in the oral cavity was about 30% of the dose. Slow absorption or clearance of drug from target tissues was observed over time. Use of the inhalation spacer caused statistically significant increases in all target tissues (factor of 2-5) and a roughly 40% decrease in oral deposition. Measurable amounts of the drug remained in target regions throughout the scanning period. CONCLUSION: Local pulmonary distribution and kinetics of inhaled drugs can be measured accurately by PET for drug development. The integrated actuator-spacer significantly enhanced deposition of TAA in target tissues and reduced deposition in the oropharyngeal region.

Administration, Inhalation↗

Tri-Nasal triamcinolone acetonide nasal spray 200 and 400 micrograms qd versus placebo and Nasacort triamcinolone acetonide nasal aerosol 440 micrograms qd in patients suffering from seasonal allergic rhinitis during the grass season.

Tri-Nasal Nasal Spray is an investigational solution of triamcinolone acetonide (TAA) currently being evaluated as a treatment for allergic rhinitis. The safety and efficacy of 200 and 400 micrograms once daily doses of Tri-Nasal Nasal Spray, an active control (440 micrograms once daily of Nasacort Nasal aerosol), and Tri-Nasal Nasal Spray placebo were compared over a 2-week treatment period in a double-blind (the Nasacort treatment was not blinded), parallel design trial. A total of 377 adult patients in 13 centers were enrolled during the grass pollen season. The primary efficacy variable was the weekly average of the SSI (Symptom Severity Index), the sum of daily nasal congestion, rhinorrhea, and sneezing severity scores from the patient diary. A total of 355 patients completed the study. All active treatments were significantly more effective than placebo in relieving nasal symptoms at each treatment week. The 400 micrograms Tri-Nasal Nasal Spray and Nasacort treatments had a rapid onset of action, demonstrating significant improvement in the SSI versus placebo by the second day of treatment. Results for the individual nasal symptoms and other secondary efficacy measures paralleled those of the primary efficacy variables. Tri-Nasal Nasal Spray and Nasacort were comparable in safety, and in treating the nonocular symptoms of seasonal allergic rhinitis.

Administration, Intranasal↗

Mometasone furoate ointment and cream 0.1 percent in treatment of psoriasis: comparison with ointment and cream formulations of fluocinolone acetonide 0.025 percent and triamcinolone acetonide 0.1 percent.

Mometasone furoate (Elocon) is a newly formulated and unique medium-potency synthetic 17-heterocyclic corticosteroid. The efficacy and safety of the ointment and cream formulations (0.1 percent) of the corticosteroid, administered once daily, were compared with those of the ointment and cream formulations of fluocinolone acetonide 0.025 percent administered three times daily and triamcinolone acetonide 0.1 percent administered twice daily in four multicenter clinical studies. They were conducted involving psoriasis patients with chronic and moderate to severe disease. Evaluation of change in disease sign scores indicated that mometasone ointment, applied once daily, was significantly more effective (P less than 0.01) than fluocinolone ointment, applied three times daily, and triamcinolone ointment, applied twice daily. The cream formulation of mometasone was significantly more effective (p less than 0.001) than fluocinolone cream, applied three times daily, and equivalent to triamcinolone cream, applied twice daily. The incidence of local adverse experiences following treatment with the ointment or cream formulations of mometasone was minimal. Mometasone ointment and cream provide a highly effective once-a-day treatment for moderate to severe psoriasis with minimal risk of side effects.

Administration, Topical↗

A pharmacokinetic study to evaluate the absolute bioavailability of triamcinolone acetonide following inhalation administration.

Triamcinolone acetonide is a glucocorticoid administered by oral inhalation in the management of asthma. With oral inhalation of glucocorticoids, systemic absorption can come from oropharyngeal, gastrointestinal, or airway deposition of the drug. The objectives of this study were to determine the absolute bioavailability of triamcinolone acetonide following inhalation administration and to delineate the airway contribution of triamcinolone acetonide absorption relative to the absolute bioavailability. All subjects received a 5-minute 400 mcg intravenous infusion of triamcinolone acetonide and a single 800 mcg dose of inhaled triamcinolone acetonide with and without oral charcoal administration in a randomized three-way crossover fashion. The oral charcoal allowed for isolating the pulmonary component of absorption by adsorbing the oropharyngeal and gastrointestinal deposited drug. The mean (+/- SD) absolute bioavailability value for inhaled triamcinolone acetonide was 25% (8.75%). Delineation of the airway contribution of triamcinolone acetonide absorption showed that 10.4% of an inhaled dose is absorbed as triamcinolone acetonide from the lungs. Mean (+/- SD) total body clearance was rapid at 0.57 (0.12) L/hr/kg. The mean (+/- SD) apparent volume of distribution following the intravenous dose was a low 1.96 (0.31) L/kg. No significant differences were noted in the apparent terminal elimination half-life of triamcinolone acetonide (approximately 2.4 hr) between treatments.

Administration, Inhalation↗

A rabbit model for assessing the ocular barriers to the transscleral delivery of triamcinolone acetonide.

Transscleral delivery of triamcinolone acetonide into the vitreous using sub-Tenon's injections may be a safer alternative to reduce the sight-threatening complications of direct intravitreal injections. However, sub-Tenon's injections have demonstrated low and poorly sustained vitreous drug levels in animal studies. To improve our understanding of the clearance mechanisms of corticosteroids, we evaluated vitreous drug levels following sub-Tenon's injection of triamcinolone acetonide in rabbits with selective elimination of conjunctival lymphatic/blood vessels and the choroid. Pigmented rabbits were given a sub-Tenon's injection of a preservative-free triamcinolone acetonide formulation of either a 10- or 20-mg dose in the superotemporal quadrant. The effect eliminating both conjunctival and choroidal clearance was evaluated by injecting the drug, followed by immediate euthanasia, effectively terminating both lymph and blood flow in the conjunctiva and choroid. To inhibit only the clearance from conjunctival lymphatics/blood vessels of a sub-Tenon's injection of triamcinolone acetonide, a group of rabbits had a 'conjunctival window' created by incising an 7 mmx7 mmx7 mm square through the conjunctiva to bare sclera in the superotemporal quadrant. To eliminate only the clearance of drug from the choroidal circulation, cryotherapy was performed in another group of rabbits creating a chorioretinal scar in the superotemporal quadrant. Following the sub-Tenon's drug injection, the eyes were enucleated in all groups after 3 hr and vitreous drug levels were measured with HPLC. In normal animals, a 10-mg sub-Tenon's injection showed no detectable vitreous drug levels; however, a 20-mg injection showed positive vitreous drug levels. This suggested that collectively, the transscleral clearance mechanisms inhibiting delivery into the vitreous may be saturated with a drug depot that has a higher release rate. A 10-mg sub-Tenon's drug depot was able to deliver drug into the vitreous when both the conjunctival and choroidal drug clearance was eliminated by euthanizing the animal immediately following the drug injection. In rabbits that had only a 'conjunctival window', selectively eliminating conjunctival drug clearance, vitreous drug levels were detected. However, in rabbits that had only cryotherapy, selectively eliminating choroidal drug clearance, vitreous drug levels were not detected suggesting that the conjunctival lymphatics/blood vessels may be an important barrier to the transscleral delivery of triamcinolone acetonide. Variability in the vitreous drug levels between rabbits in each group precluded statistical testing. In summary, the rabbit appeared to demonstrate saturable ocular barriers to transscleral delivery of triamcinolone acetonide into the vitreous following a sub-Tenon's injection. The results suggested that the conjunctival lymphatics/blood vessels may be an important barrier to the delivery of triamcinolone acetonide to the vitreous in this rabbit model. The barrier location and clearance abilities of the ocular tissues are important to consider when developing a successful transscleral drug delivery system. Animal models, retaining the dynamics of blood and lymph flow, may improve the basic understanding of the ocular barriers involved with transscleral drug transport and warrants further investigation.

Animals↗

Intra-articular therapy of experimental arthritis with a derivative of triamcinolone acetonide incorporated in liposomes.

Triamcinolone acetonide-21-palmitate was synthesized and incorporated into liposomes for intra-articular treatment of an experimentally-induced arthritis in the knee joints of rabbits. The liposomal formulation was more efficient than free triamcinolone acetonide in solution in suppressing the arthritis. Using radioactive tracers, it was found that triamcinolone acetonide-21-palmitate incorporated into liposomes was retained in the articular cavity, together with the liposomal lipids, for a much longer period than free triamcinolone acetonide, and this correlated with its anti-inflammatory effect.

Animals↗

The influence of hydrocolloid patch composition on the bioavailability of triamcinolone acetonide in humans.

Triamcinolone acetonide (TACA) is a corticosteroid; it is used in the systemic and topical treatment of a variety of inflammatory conditions, including eczema and psoriasis. Conventionally, for topical use, the drug is formulated in a cream or ointment. However, it has been observed in vitro that percutaneous penetration of corticosteroids can be influenced by hydrocolloid patches. Corticosteroids produce a pallor or blanching when applied to the skin that correlates with anti-inflammatory activity; this property has been used extensively as a bioassay. The aim of this study therefore was to evaluate the occlusive properties of a range of hydrocolloid patches containing TACA on the drug's penetration in vivo using visual assessment and a graded multiple measurement. The in vivo hydration of these dermatological patches was also investigated. Statistical analysis of the weight gains of patches containing either NaCMC 39% or pectin 39% showed that there was a significant difference in the rates of hydration of the two types of patch (p < .005). An increase in application time of the hydrocolloid patches allowed more TACA to be released, which was illustrated by an increase in both the maximum percentage total possible score (%TPS) values and AUC, although changes in the hydrocolloid composition did not significantly alter the blanching response. All of the patches adhered well, were unobtrusive to the normal activity of the wearers, and showed great potential for the convenient, localized, prolonged delivery of drugs to the skin.

Administration, Cutaneous↗

Pharmacokinetics of triamcinolone acetonide and its phosphate ester.

Triamcinolone acetonide in the form of its phosphate ester was given intravenously in two different doses (10 mg/kg and 80 mg). Plasma levels of the ester and triamcinolone acetonide were measured and pharmacokinetic parameters were calculated. The pharmacokinetics both of the phosphate and the free alcohol were dose-dependent. No unchanged ester was found in the urine, indicating complete conversion of the pro-drug. Triamcinolone was not a major metabolite of triamcinolone acetonide in humans. Renal clearance was low and independent of the dose. Only about 1% of the dose was found in the urine as triamcinolone acetonide.

Adult↗

Renal effects of long term administration of triamcinolone acetonide in normal dogs.

Triamcinolone acetonide was administered in excessive dosage to dogs to study the renal mechanism responsible for polyuria which is a clinically undesirable side effect of long term glucocorticoid therapy.Polyuria occurred coincident with a significant increase in urinary solute output. Although continuous administration of triamcinolone acetonide at 0.1 or 0.2 mg/lb/day caused a small but significant increase in creatinine output, the primary mechanism for the polyuria was increased solute excretion. Associated with the polyuria was pronounced hyperphagia and polydipsia. The cause of the hyperphagia was not established. The increase in electrolyte excretion caused by this synthetic steroid was probably compensated for by the hyperphagia. Because all the dogs showed muscle weakness and loss of body condition, it is likely that alteration in protein and amino acid metabolism was responsible for the hyperphagia.

Animals↗