title: Assessment of glucocorticoid lung targeting by ex-vivo receptor binding studies in rats.
abstract: Triamcinolone acetonide (TA, 22 micrograms) was given to rats by intravenous (i.v.) injection or intratracheal (IT) instillation. Free glucocorticoid receptors were monitored over time in liver and lung using an ex-vivo receptor binding technique. After i.v. administration of a TA solution, the reduction of free receptors over time was very similar in lung and liver (AUCLung = 280 +/- 47% h; AUCLiver = 320 +/- 76% h). Intratracheal instillation of the same solution produced time profiles which mirrored those of i.v. injection (AUCLung = 260 +/- 41% h; AUCLiver = 330 +/- 50% h). The lack of lung targeting was also reflected in the failure to show any significant difference in the pulmonary targeting factor T (AUCLung/AUCLiver) between i.v. (T = 0.84 +/- 0.18) and IT (T = 0.78 +/- 0.03) administration. In contrast, a certain degree of lung specificity was observed after IT instillation of a glucocorticoid suspension (22 micrograms; AUCLung = 160 +/- 135% h; AUCLiver = 65 +/- 91% h, T = 2.3 +/- 0.5) as indicated by significant differences in T between i.v. injection and IT instillation (p = 0.038). The method presented provides a means of simultaneously assessing pulmonary and systemic effects after different forms and routes of administration and might be of value in further studying multiple aspects of inhalation glucocorticoid therapy.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville 32610, USA.
authors.forename: G
authors.initials: G
authors.lastname: Hochhaus
authors.forename: R J
authors.initials: RJ
authors.lastname: Gonzalez-Rothi
authors.forename: A
authors.initials: A
authors.lastname: Lukyanov
authors.forename: H
authors.initials: H
authors.lastname: Derendorf
authors.forename: H
authors.initials: H
authors.lastname: Schreier
authors.forename: T
authors.initials: T
authors.lastname: Dalla Costa
mesh_terms: D000818:Animals; D002244:Carbon; D004396:Coloring Agents / Q000493:pharmacokinetics; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology; D007275:Injections, Intravenous; D007322:Instillation, Drug; D007700:Kinetics; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D009928:Organ Specificity; D051381:Rats; D011916:Rats, Inbred F344; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism*; D012996:Solutions; D013535:Suspensions; D014132:Trachea; D014222:Triamcinolone Acetonide / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D004396:Coloring Agents; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D012996:Solutions; D013535:Suspensions; C028433:chinese ink; D002244:Carbon; D014222:Triamcinolone Acetonide