Document Detail


Pharmacodynamics and pharmacokinetics of inhaled iloprost, aerosolized by three different devices, in severe pulmonary hypertension.
MedLine Citation:
PMID:  14555558     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Inhalation of iloprost, a stable prostacyclin analog, is an effective therapy for pulmonary hypertension with few side effects. This approach may, however, be handicapped by limitations of currently available nebulization devices. We assessed whether the physical characterization of a device is sufficient to predict drug deposition and pharmacologic effects. METHODS: We investigated the effects of a standardized iloprost aerosol dose (5 micro g; inhaled within approximately 10 min) in 12 patients with severe pulmonary hypertension in a crossover design employing three well-characterized nebulizers. The nebulizers use different techniques to increase efficiency and alveolar targeting (Ilo-Neb/Aerotrap [Nebu-Tec; Elsenfeld, Germany], Ventstream [MedicAid; Bognor Regis, UK], and HaloLite [Profile Therapeutics; Bognor Regis, UK]). Measurements were performed using a Swan-Ganz catheter and determination of arterial iloprost plasma levels. RESULTS: During inhalation of iloprost, the pulmonary vascular resistance decreased substantially (baseline, approximately 1,250 dyne.s.cm(-5); decrease, - 35.5 to - 38.0%) and pulmonary artery pressure decreased substantially (baseline, approximately 58 mm Hg; decline, - 18.4 to -21.8%), whereas the systemic arterial pressure was largely unaffected. Cardiac output and mixed venous and arterial oxygen saturation displayed a marked increase. The pharmacodynamic profiles with the three devices were superimposable. Moreover, rapid entry of iloprost into the systemic circulation was noted, peaking immediately after termination of the inhalation maneuver, with very similar maximum serum concentrations (158 pg/mL, 155 pg/mL, and 157 pg/mL), and half-lives of serum levels (6.5 min, 9.4 min, and 7.7 min) for the three nebulizers, respectively. Interestingly, the "half-life" of the pharmacodynamic effects in the pulmonary vasculature (eg, decrease in pulmonary vascular resistance, ranging between 21 and 25 min) clearly outlasted this serum level-based pharmacokinetic half-life. CONCLUSIONS: A standardized dose of aerosolized iloprost delivered by different nebulizer types induces comparable pharmacodynamic and pharmacokinetic responses. Pulmonary vasodilation, persisting after disappearance of the drug from the systemic circulation, supports the hypothesis that local drug deposition largely contributes to the preferential pulmonary vasodilation in response to inhaled iloprost.
Authors:
Horst Olschewski; Beate Rohde; Jürgen Behr; Ralph Ewert; Tobias Gessler; H Ardeschir Ghofrani; Thomas Schmehl
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Publication Detail:
Type:  Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chest     Volume:  124     ISSN:  0012-3692     ISO Abbreviation:  Chest     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-10-13     Completed Date:  2003-12-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0231335     Medline TA:  Chest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1294-304     Citation Subset:  AIM; IM    
Affiliation:
Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany. horst.olschewski@innere.med.uni-giessen.de
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MeSH Terms
Descriptor/Qualifier:
Administration, Inhalation
Adult
Aged
Cross-Over Studies
Equipment Design
Female
Humans
Hypertension, Pulmonary / drug therapy*
Iloprost / administration & dosage,  pharmacology*
Male
Middle Aged
Nebulizers and Vaporizers*
Severity of Illness Index
Vasodilator Agents / administration & dosage,  pharmacology*
Chemical
Reg. No./Substance:
0/Vasodilator Agents; 78919-13-8/Iloprost

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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