Kenalog
The effect of intravitreal triamcinolone acetonide on intraocular pressure.

Bakri SJ, Beer PM.

Lions Eye Institute, Albany Medical College, 35 Hackett Boulevard, Albany, NY 12208, USA.

BACKGROUND AND OBJECTIVE: To ascertain whether a single 4-mg intravitreal triamcinolone acetonide injection is associated with elevated intraocular pressure (IOP). PATIENTS AND METHODS: Retrospective noncomparative interventional case series. Forty-three consecutive eyes of 38 patients who had 12 weeks of follow-up were included. The IOPs before and after triamcinolone acetonide treatment were recorded by Goldmann applanation at each patient visit. RESULTS: Within 12 weeks after intravitreal triamcinolone acetonide injection, 21 of 43 eyes (48.8%) demonstrated an increase in IOP of 5 mm Hg or greater, and 12 of 43 eyes (27.9%) had an increase in IOP of 10 mm Hg or greater. The mean time for an increase in IOP of 5 mm Hg or greater to occur was 4.1 weeks (standard deviation = 4.8 weeks), and the mean time to reach maximum IOP was 6.6 weeks (standard deviation = 5.1). The difference between the mean pre-injection IOP (15.12 mm Hg, n = 43) and the maximum post-injection IOP (20.74 mm Hg, n = 43) was statistically significant (P < .0001). CONCLUSION: A single 4-mg intravitreal triamcinolone acetonide injection is associated with an increase in IOP of 10 mm Hg or greater in 27.9% of eyes after the first injection. All eyes responded to topical glaucoma medication.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14509462&dopt=Abstract triamcinolone Kenalog



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Effect of dose and release rate on pulmonary targeting of liposomal triamcinolone acetonide phosphate.

Suarez S, Gonzalez-Rothi RJ, Schreier H, Hochhaus G.

Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville 32610, USA.

PURPOSE: To demonstrate the importance of dose and drug release rate for pulmonary targeting of inhaled glucocorticoids using an animal model of intrapulmonary drug deposition. METHODS: Liposomes composed of 1,2-distearoyl phosphatidylcholine (DSPC), 1,2-distearoyl phosphatidylglycerol (DSPG) and triamcinolone acetonide phosphate (TAP) or liposomes containing triamcinolone acetonide (TA) were prepared by a mechanical dispersion method followed by extrusion through polycarbonate membranes. Encapsulation efficiency was assessed after size exclusion gel chromatography by reverse phase HPLC. The effect of liposome size (200 nm and 800 nm) on the release kinetics of water-soluble encapsulated material was determined in vitro at 37 degrees C using 6-carboxyfluorescein as a marker and Triton X-100 (0.03%) as a leakage inducer. To investigate the relationship between drug release and pulmonary targeting, 100 micrograms/kg of TAP in 800 nm liposomes was delivered to male rats by intratracheal instillation (IT) and the results compared to data for 100 micrograms/kg TA liposomes (recently shown to exhibit a rapid drug release under sink conditions) and to previous studies reported for an equal dose of TAP in solution and TAP in 200 nm (1). Pulmonary targeting was assessed by simultaneously monitoring glucocorticoid receptor occupancy over time in lung and liver using an ex vivo receptor binding assay as a pharmacodynamic measure of glucocorticoid action. To assess the effect of dose on pulmonary targeting experiments were performed using 2.5, 7.5, 25, 100, and 450 micrograms/kg of TAP in 800 nm liposomes. RESULTS: The in vitro efflux of 6-carboxyfluorescein from (DSPC:DSPG) liposomes after exposure to Triton-X was biexponential. The terminal half-lives of 3.7 h and 9.0 h for the 200 nm and 800 nm liposomes, respectively, demonstrated that larger liposomes promote slower release of encapsulated water-soluble solute while previous results already indicated that encapsulation of lipophilic TA does not result in sustained release. Pulmonary targeting, defined as the difference between cumulative lin and liver receptor occupancies was most pronounced for the 800 nm liposomes (370%xh), followed by the 200 nm preparation (150%xh). No targeting was observed for TAP in solution (30%xh) or the rapid releasing TA liposome preparation. Correspondingly, the mean pulmonary effect time (MET) increased from 2.4-3.0 hr for TA liposomes or TAO in solution to 5.7 h and > 6.2 h for TAP in 200 nm and in 800 nm liposomes, respectively. Escalating doses of TAP encapsulated in 800 nm liposomes revealed a distinct bell shaped relationship between the TAP dose and pulmonary targeting with a maximum occurring at 100 micrograms/kg (370%xh). CONCLUSIONS: The in vivo data presented here confirm that pulmonary residence time and dose affect the extent of lung targeting of glucocorticoids delivered via the lung.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9563078&dopt=Abstract triamcinolone Kenalog



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Contractile properties and histochemical characteristics of the rat diaphragm after prolonged triamcinolone treatment and nutritional deprivation.

Koerts-De Lang E, Schols AM, Wouters EF, Gayan-Ramirez G, Decramer M.

Department of Pulmonology, Maastricht University, The Netherlands.

The influence of decreased muscle mass and reduced food intake on diaphragm structure and contractility in male Wistar rats was determined after triamcinolone acetate treatment (TR: 0.5 mg per kg per day for 4 weeks) and two degrees of undernutrition (PW: pair-weight, which resulted in a similar (41%) reduction of body weight as TR; PF: pair-fed, which resulted in a moderate (13%) reduction of body weight) and a free-fed control group (FF, with an increase (9%) in body weight). energy intake of TR decreased, but based on daily measurements of food intake and body weight, energy expenditure of the TR rats was increased compared with the other groups. Body (BW) and muscle weights were reduced in proportion to the extent of undernutrition in the nutritionally deprived rates (i.e. BW and diaphragm weight of PF animals were reduced 215 and 16% respectively compared with FF, v. a. 48% and 41% reduction in the PW group). Triamcinolone-induced atrophy was limited to type II fibres (30% of type IIa and 45% of type IIx/b, p < 0.05), while severe chronic undernutrition (PW) induced a generalized fibre type atrophy in the diaphragm (23% type I, 38% type IIa and 49% type IIx/b, p < 0.05), and moderate undernutrition (PF) caused only significant type IIa atrophy (20%, p < 0.05). A leftward shift of the diaphragmatic tension-frequency relationship and a decreased fatiguability of the TR and PW bundles were observed (p < 0.01), while the PF bundles were not significantly different compared with FF. These results suggest that triamcinolone and severe undernutrition cause similar alterations in in vitro contractility of the diaphragm. The effects of triamcinolone treatment on diaphragm structure may be partly explained by the reduced food intake, but the atrophy pattern induced by severe undernutrition (PW) was different.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9682141&dopt=Abstract triamcinolone Kenalog



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Effect of long-term glucocorticoid treatment on oestradiol-induced proliferation in the uterus of ovariectomized rats.

Gunin AG.

Department of Histology, Medical Institute of Chuvash State University, Cheboksary, Russia.

The aim of this study was to examine the effect of long-term treatment with glucocorticoids on the uterine response to oestradiol. Ovariectomized rats were treated with crystal triamcinolone acetonide (0.1 mg/100 g, i.m.) or saline (0.1 ml/100 g i.m.) for 29 days. Over this period five injections were administered, one per week. On the second day after the last triamcinolone injection, rats were treated with a single injection of oestradiol dipropionate (5 micrograms/100 g, s.c.) or vehicle (olive oil, 0.1 ml/100 g, s.c.). The effects of oestradiol in the uterus were determined by measuring mitotic index, bromodeoxyuridine (BrdU)-labelling index (BrdU was injected 2 h before the rats were killed; 2 mg/100 g, i.p.), and proliferating cell nuclear antigen (PCNA)-labelling index 24, 36 and 48 h after the injection of oestradiol or vehicle. Long-term treatment with glucocorticoids resulted in dissimilar changes in oestradiol-induced proliferation in epithelial and connective-tissue (stroma) components of the uterus. In luminal and glandular epithelia, there was an initial reduction in proliferation at 24 h, followed by an increase at 36 h and a further reduction at 48 h after the oestradiol injection. In stromal cells of the endometrium, triamcinolone treatment caused a large constant increase in oestradiol-induced proliferation throughout the experiment. The glucocorticoid treatment had no effect on the parameters without oestradiol administration.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9691981&dopt=Abstract triamcinolone Kenalog



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Intravitreal triamcinolone for choroidal neovascularization in ocular histoplasmosis syndrome.

Rechtman E, Allen VD, Danis RP, Pratt LM, Harris A, Speicher MA.

Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

PURPOSE: To report the effects of intravitreal triamcinolone acetonide injections for subfoveal and juxtafoveal choroidal neovascularization (CNV) in ocular histoplasmosis syndrome. METHODS: In a retrospective analysis, the proportion of eyes that gained >or=5 or lost >or=5 and >or=15 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, best-corrected visual acuity using ETDRS letter score (VA), greatest linear dimension (GLD), and treatment side effects were assessed. RESULTS: Ten patients (five subfoveal, five juxtafoveal CNV; median follow-up: 17 months; range, 6-41 months) were evaluated. Thirty percent gained >or=5 letters, 20% lost 5 to 14 letters, and 50% maintained stable VA. Overall, mean VA and GLD remained stable. Side effects were transient intraocular pressure elevation and mild cataract development. CONCLUSIONS: Intravitreal triamcinolone acetonide for CNV resulting from OHS was found to be relatively safe and showed good visual outcome for both subfoveal and juxtafoveal CNV. Further studies are warranted to evaluate this treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14516819&dopt=Abstract triamcinolone Kenalog



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Biodistribution and kinetics of nasal carbon-11-triamcinolone acetonide.

Berridge MS, Heald DL, Muswick GJ, Leisure GP, Voelker KW, Miraldi F.

Case Western Reserve University/University Hospitals of Cleveland, Division of Radiology, Ohio 44106, USA.

PET is a technique with a strong potential for use in drug evaluation and development. In particular, the distribution and pharmacokinetics of locally administered drugs may be advantageously explored noninvasively using labeled compounds. This pilot study was performed to demonstrate the effectiveness of PET for drug development and to determine the human biodistribution and kinetics of triamcinolone acetonide, labeled with 11C, formulated and nasally administered as Nasacort AQ nasal inhalant. METHODS: Carbon-11-labeled triamcinolone acetonide was formulated as the commercial product, and PET scans of the heads of four volunteers were performed in a vertical orientation. Region-of-interest analysis with MRI coregistration was used to analyze the distribution and kinetics in nasal tissues. RESULTS: Deposition of the majority of the dose on target tissues was immediate. Penetration into sinuses was observed. There was moderate redistribution and slow migration of the drug through nasal passages to the throat. Significant amounts of the drug remained in target regions for several hours. CONCLUSION: PET is an effective means to determine local drug distribution and kinetics.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9829591&dopt=Abstract triamcinolone Kenalog