Pharmacokinetics of Triamcinolone Acetonide After Intravenous, Oral, and Inhaled Administration

Derendorf, Hartmut; Hochhaus, Günther; Rohatagi, Shashank; Möllmann, H; Barth, Jürgen; Sourgens, H.; Erdmann, M.

doi:10.1002/j.1552-4604.1995.tb04064.x

Cited by 103 publications

(59 citation statements)

References 4 publications

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“…This protein-binding, generally to albumin, is rapid and reversible. The extent of protein-binding ranges 71-99% among currently available ICS (table 3) [21,35,[46][47][48][49][50][51][52][53]66]. The degree of protein-binding of these rapidly metabolised corticosteroids controls their unbound systemic concentrations and limits their systemic side-effects, since only the free drug is pharmacologically active.…”

Section: Protein-bindingmentioning

confidence: 99%

Relevance of pharmacokinetics and pharmacodynamics of inhaled corticosteroids to asthma

Derendorf

Nave²,

Drollmann

et al. 2006

European Respiratory Journal

216

182

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The pharmacokinetic and pharmacodynamic effects of inhaled corticosteroids (ICS) have shaped the efficacy and safety of these agents in the treatment of asthma.Important pharmacokinetic and pharmacodynamic characteristics that can enhance the efficacy of ICS include small particle size, high glucocorticoid-receptor-binding affinity, long pulmonary residence time and lipid conjugation. These characteristics can increase or prolong the antiinflammatory effects of an ICS. Important pharmacokinetic characteristics that can enhance the safety of ICS include on-site activation in the lung, low oropharyngeal exposure, negligible oral bioavailability, high protein-binding and rapid systemic clearance.The degree of oropharyngeal exposure is relevant to local side-effects, such as oropharyngeal candidiasis, dysphonia and coughing. Pharmacokinetic properties that influence the degree of systemic exposure are relevant to the pharmacodynamic effect of ICS-induced hypothalamicpituitary-adrenal axis suppression and cortisol suppression, an indicator of potential long-term systemic side-effects, such as reduced growth velocity and bone density, fractures, and skin bruising and thinning.Therefore, significant differences in the pharmacokinetic and pharmacodynamic characteristics of the currently available inhaled corticosteroids warrant careful consideration when used in clinical practice as they may result in differences in efficacy and local and systemic safety profiles.

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Section: Protein-bindingmentioning

confidence: 99%

Relevance of pharmacokinetics and pharmacodynamics of inhaled corticosteroids to asthma

Derendorf

Nave²,

Drollmann

et al. 2006

European Respiratory Journal

216

182

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“…Fluticasone propionate has an elimination half-life of 14.4 hours, which is considerably longer than that of other corticosteroids, including budesonide (2.3 hours), triamcinolone (3.6 hours), flunisolide (1.6 hours) and beclomethasone monopropionate (6.5 hours). 12,14,17,[19][20][21] Thus, with a 12-hour dosing interval for fluticasone, the average plasma concentration is approximately 1.7 times higher after repeated dosing compared with single dosing. 12 This degree of steady state accumulation with fluticasone is in keeping with a 2-fold increase in adrenal suppression between single-and repeated-dose administration.…”

Section: Pharmacologic and Pharmacokinetic Determinantsmentioning

confidence: 99%

Systemic Adverse Effects of Inhaled Corticosteroid Therapy

1999

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Objective: To appraise the data on systemic adverse effects of inhaled corticosteroids.Methods: A computerized database search from January 1, 1966, through July 31, 1998, using MEDLINE, EMBASE, and BIDS and using appropriate indexed terms. Reports dealing with the systemic effects of inhaled corticosteroids on adrenal gland, growth, bone, skin, and eye, and reports on pharmacology and pharmacokinetics were reviewed where appropriate. Studies were included that contained evaluable data on systemic effects in healthy volunteers as well as in asthmatic children and adults. A statistical meta-analysis using regression was performed for parameters of adrenal suppression in 27 studies.Results: Marked adrenal suppression occurs with high doses of inhaled corticosteroid above 1.5 mg/d (0.75 mg/d for fluticasone propionate), although there is a considerable degree of interindividual susceptibility. Metaanalysis showed significantly greater potency for doserelated adrenal suppression with fluticasone compared with beclomethasone dipropionate, budesonide, or triamcinolone acetonide, whereas prednisolone and fluticasone propionate were approximately equivalent on a 10:1-mg basis. Inhaled corticosteroids in doses above 1.5 mg/d (0.75 mg/d for fluticasone propionate) may be associated with a significant reduction in bone density, although the risk for osteoporosis may be obviated by postmenopausal estrogen replacement therapy. Although medium-term growth studies showed suppressive effects with 400-µg/d beclomethasone dipropionate, there was no evidence to support any significant effects on final adult height. Long-term, high-dose inhaled corticosteroid exposure increases the risk for posterior subcapsular cataracts, and, to a much lesser degree, the risk for ocular hypertension and glaucoma. Skin bruising is most likely to occur with high-dose exposure, which correlates with the degree of adrenal suppression.Conclusions: All inhaled corticosteroids exhibit doserelated systemic adverse effects, although these are less than with a comparable dose of oral corticosteroids. Metaanalysis shows that fluticasone propionate exhibits greater dose-related systemic bioactivity compared with other available inhaled corticosteroids, particularly at doses above 0.8 mg/d. The long-term systemic burden will be minimized by always trying to achieve the lowest possible maintenance dose that is associated with optimal asthmatic control and quality of life. Med. 1999;159:941-955 Arch Intern

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“…It has a prolonged elimination due to equilibrium between the tissue and blood compartments (Thorsson et al, 1997). In comparison, less lipophilic glucocorticoids such as triamcinolone acetonide exhibit preferential partitioning into the blood as compared with the systemic tissue compartment, resulting in a smaller volume of distribution and a shorter elimination half-life which makes it more effective (Derendorf et al, 1995).…”

Section: Glucocorticoidsmentioning

confidence: 99%