A Pharmacokinetic Study to Evaluate the Absolute Bioavailability of Triamcinolone Acetonide following Inhalation Administration

Argenti, Domenick; Shah, Bharti; Heald, Donald

doi:10.1177/00912709922008335

Cited by 23 publications

(12 citation statements)

References 11 publications

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“…In particular, the spacer was shown to have a strong, favorable, and highly significant effect on the deposition pattern of the drug, something which had not previously been determined. Agreement was noted between regional deposition and absorption kinetics, in units of micrograms of active ingredient, and independent pharmacokinetic data [Argenti et al, 1999]. Additional nasal inhalation studies with the same drug and with […”

Section: Different Formulations Included Investigations Into the Antimentioning

confidence: 66%

Imaging studies of biodistribution and kinetics in drug development

Berridge

Heald²,

Lee

2003

Drug Development Research

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Although the intravenous route of administration is rarely used for drugs, it is by far the most common route for PET and SPECT radiotracers. This article discusses the use of planar and tomographic nuclear medicine technologies to image and quantify the distribution of drugs after local administration. In principle, this would include topical dermatologic, otic, ophthalmic, rectal, and vaginal administration, as well as the intramuscular, oral, and inhalation routes, although precedents do not yet exist for all of these. The studies reviewed focus mainly on oral ingestion and oral and nasal inhalation. The use of nondrug tracers for formulations is discussed, principally with planar imaging or SPECT using radionuclides such as 99m Tc, as well as PET imaging where the active ingredient of a formulation can be labeled with 11 C or sometimes 18 F. An example of the latter type is a study of the deposition and kinetics in the lungs and airways of triamcinolone acetonide, an antiinflammatory steroid used for topical treatment of allergic rhinitis and asthma, dispensed from an inhaler. PET has high potential for evaluation of different formulations and delivery devices in the development of topically applied drugs. Drug Dev.

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Section: Different Formulations Included Investigations Into the Antimentioning

confidence: 66%

Imaging studies of biodistribution and kinetics in drug development

Berridge

Heald²,

Lee

2003

Drug Development Research

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“…Meanwhile, in humans, a difference surely exists between such different-sized aerosol inhalations, in both local and systemic responses (Adjei and Garren 1990;Terzano et al 2001). Thus, attempts to estimate the lung-regionspecific bioavailability following oral inhalation must be made in humans and, in fact, similar oral charcoal treatment has been employed to diminish GI absorption for drugs and solutes that are mucociliarly cleared by the lung (Argenti et al 1999;Daley-Yates et al 2001;Lipworth 1996). It should be noted, however, that this approach should be only limited to the drugs and solutes that have been approved for human application and, thus, is uncommonly applicable.…”

Section: Discussionmentioning

confidence: 99%

Fractional contribution of lung, nasal and gastrointestinal absorption to the systemic level following nose-only aerosol exposure in rats: a case study of 3.7-µm fluorescein aerosols

et al. 2003

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Because absorption takes place from multiple sites of aerosol deposition, it is generally difficult to interpret systemic levels following nose-only inhalation in laboratory rodents. Therefore, this study attempted to determine the fractional contribution of lung, nasal and gastrointestinal (GI) absorption to the observed systemic level following nose-only aerosol exposure in rats using fluorescein as a model powder solute. Rats were treated orally with vehicle or activated charcoal, the latter diminishing GI absorption of fluorescein, and were subsequently nose-only exposed to 3.7- micro m fluorescein aerosols at 25.2 micro g/l(air) for 10 min. While fluorescein similarly disappeared from the lung at a half-life of 0.23 hr, its plasma concentrations in the charcoal-treated group were significantly lower than those in the charcoal-untreated (vehicle) group. This suggests that significant portions of fluorescein were transported by nasopharyngeal and tracheobronchial mucociliary clearances following aerosol exposure and were absorbed from the GI tract. Despite the lack of GI absorption in the charcoal-treated animals, it was estimated that this nose-only exposure of fluorescein allowed 25.7 and 82.5 micro g/kg of simultaneous lung and nasal deposition, respectively, followed by their absorption composing the observed systemic level in this group (AUC(0- infinity ) 137.49 ng/ml h). Thus, assuming linear pharmacokinetics of fluorescein, the extent of absorption (AUC(0- infinity )) due to such nasal deposit (82.5 micro g/kg) was estimated to be 47.00 ng/ml h using the AUC(0- infinity ) obtained in an independent study of intranasal powder insufflation at 34.5 micro g/kg in the charcoal-treated rats (AUC(0- infinity ) 19.66 ng/ml h). As a result, the AUC(0- infinity ) due to 25.7 micro g/kg of the lung deposit was deconvoluted to be 90.49 ng/ml h and finally, the absolute bioavailability (F%) of the "lung-region-specific" deposition and absorption of fluorescein was estimated to be 55.0%. It is observed therefore, that lung, nasal and GI absorption accounted for 24.2, 12.5 and 63.3% of the total fluorescein absorption, respectively, following nose-only exposure of 3.7- micro m aerosols. This study addresses the common methodological insufficiency of nose-only inhalation studies in rodents, which have been neglected in most cases, and provides the appropriate kinetic interpretation for their observed systemic level.

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“…In this study, we only analyzed the deviation of F based on the two-compartment model. As a result, 10 data sets, 2 of which were original data from published literature [6] and 8 of which were transformed from the plasma concentration-time graphs [5,[7][8][9][10][11][12], met the preconditions and were further analyzed.…”

Section: Methodsmentioning

confidence: 99%

“…Regarding experimental subjects, one study used broiler chickens [11], one used Sprague-Dawley rats [12], and the rest used human subjects. All of the studies used oral administration as the ev administration method, except for one that used inhalation [7]. The information from the 10 studies are depicted in Table 2.…”

Section: Methodsmentioning

confidence: 99%

Modifications of the Method for Calculating Absolute Drug Bioavailability

et al. 2016

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-Purpose: Absolute bioavailability (F) is calculated as the ratio of the area under the plasma drug concentration-time curve (AUC) between extravascular administration and intravenous injection. However, as distribution of a drug after intravenous administration does not reach an equilibrium in the body during the distribution phase, the plasma drug concentration at this phase does not reflect the total amount of drug in the body. The goal of this paper was to analyze the insufficiencies of the method for calculating on absolute bioavailability and to propose a modification to improve the calculation. Methods: Literature reporting absolute bioavailability published during 1983-2014 was searched for ten drug candidates. Plasma drug concentrations representing the amount of drug in the body were then calculated at each time point during the distribution phase according to the plasma drug concentration-time relationship during the elimination phase. Results: The AUC values based on the distribution equilibrium drug concentrations following intravenous injection were 75%±11% of the actually measured drug concentrations in the literature. The absolute bioavailability values in the literature were 76%±12% of the actual bioavailability based on the AUCs from distribution-equilibrium drug concentrations. Conclusions: The present method underestimates the absolute drug bioavailability and should be modified to represent the data more accurately.

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A Pharmacokinetic Study to Evaluate the Absolute Bioavailability of Triamcinolone Acetonide following Inhalation Administration

Cited by 23 publications

References 11 publications

Imaging studies of biodistribution and kinetics in drug development

Imaging studies of biodistribution and kinetics in drug development

Fractional contribution of lung, nasal and gastrointestinal absorption to the systemic level following nose-only aerosol exposure in rats: a case study of 3.7-µm fluorescein aerosols

Modifications of the Method for Calculating Absolute Drug Bioavailability

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