Comparison of pharmacokinetics and vasodilatory effect of nebulized and infused iloprost in experimental pulmonary hypertension: Rapid tolerance development

Journal of Aerosol Medicine: Deposition, Clearance, and Effects in the Lung

Volumn 19, Issue 3, 2006, Pages 353-363

  Schermuly, Ralph Theo ^a,c   Schulz, Andreas ^a   Ghofrani, Hossein Ardeschir ^a   Breitenbach, Christina Susanne ^a   Weissmann, Norbert ^a   Hildebrand, Michael ^b   Kurz, Julia ^b   Grimminger, Friedrich ^a   Seeger, Werner ^a  

^a JUSTUS LIEBIG UNIVERSITY   (Germany)

^b BAYER PHARMA AG   (Germany)

^c UNIVERSITY HOSPITAL GIESSEN   (Germany)

Author keywords

Aerosol; Iloprost; Prostacyclin; Pulmonary hypertension; U46619

Indexed keywords

15 HYDROXY 11ALPHA,9ALPHA EPOXYMETHANOPROSTA 5,13 DIENOIC ACID; ILOPROST; PROSTANOID;

ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG INFUSION; DRUG TOLERANCE; FEMALE; ISOLATED LUNG; LUNG BLOOD VESSEL; MALE; NEBULIZATION; NONHUMAN; PHARMACODYNAMICS; PULMONARY HYPERTENSION; RABBIT; VASODILATATION;

15-HYDROXY-11 ALPHA,9 ALPHA-(EPOXYMETHANO)PROSTA-5,13-DIENOIC ACID; ANIMALS; DRUG TOLERANCE; EPOPROSTENOL; FEMALE; HYPERTENSION, PULMONARY; ILOPROST; LUNG; MALE; MODELS, STATISTICAL; NEBULIZERS AND VAPORIZERS; PERFUSION; RABBITS; TIME FACTORS; VASODILATOR AGENTS;

EID: 33750934586     PISSN: 08942684     EISSN: None     Source Type: Journal    
DOI: 10.1089/jam.2006.19.353     Document Type: Article

References (48)

1. Persons, D.D., G.D. Hess, W.J. Muller, et al. 1987. Airway deposition of hygroscopic heterodispersed aerosols: results of a computer calculation. J. Appl. Physiol. 63:1195-1204.
2. Rossaint, R., K.J. Falke, F. Lopez, et al. 1993. Inhaled nitric oxide for the adult respiratory distress syndrome. N. Engl. J. Med. 328:399-405.
3. Walmrath, D., T. Schneider, R. Schermuly, et al. 1996. Direct comparison of inhaled nitric oxide and aerosolized prostacyclin in acute respiratory distress syndrome. Am. J. Respir. Crit Care Med. 153:991-996.
4. Walmrath, D., T. Schneider, J. Pilch, et al. 1993. Aerosolised prostacyclin in adult respiratory distress syndrome. Lancet 342:961-962.
5. Walmrath, D., T. Schneider, J. Pilch, et al. 1995. Effects of aerosolized prostacyclin in severe pneumonia. Impact of fibrosis. Am. J. Respir. Crit Care Med. 151:724-730.
6. Zwissler, B., G. Kemming, O. Habler, et al. 1996. Inhaled prostacyclin (PGI2) versus inhaled nitric oxide in adult respiratory distress syndrome. Am. J. Respir. Crit Care Med. 154:1671-1677.
7. Barst, R.J., L.J. Rubin, W.A. Long, et al. 1996. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. The Primary Pulmonary Hypertension Study Group. N. Engl. J. Med. 334:296-302.
8. McLaughlin, V.V., D.E. Genthner, M.M. Panella, et al. Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension. N. Engl. J. Med. 338:273-277.
9. Badesch, D.B., V.F. Tapson, M.D. McGoon, et al. 2000. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann. Intern. Med. 132:425-434.
10. Olschewski, H., D. Walmrath, R. Schermuly, et al. 1996. Aerosolized prostacyclin and iloprost in severe pulmonary hypertension. Ann. Intern. Med. 124:820-824.
11. Olschewski, H., H.A. Ghofrani, D. Walmrath, et al. 1999. Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to lung fibrosis. Am. J. Respir. Crit Care Med. 160:600-607.
12. Fitscha, P., B. Tiso, and H. Sinzinger. 1987. Iloprost in peripheral vascular disease-platelet function and clinical outcome. Prog. Clin. Biol. Res. 242:463-468.
13. McHugh, N.J., M. Csuka, H. Watson, et al. 1988. Infusion of iloprost, a prostacyclin analogue, for treatment of Raynaud's phenomenon in systemic sclerosis. Ann. Rheum. Dis. 47:43-47.
14. Fiessinger, J.N., and M. Schafer. 1990. Trial of iloprost versus aspirin treatment for critical limb ischaemia of thromboangiitis obliterans. The TAO Study. Lancet 335:555-557.
15. Hoeper, M.M., M. Schwarze, S. Ehlerding, et al. 2000. Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N. Engl. J. Med. 342:1866-1870.
16. Olschewski, H., H.A. Ghofrani, T. Schmehl, et al. 2000. Inhaled iloprost to treat severe pulmonary hypertension. An uncontrolled trial. German PPH Study Group. Ann. Intern. Med. 132:435-443.
17. Olschewski, H., G. Simonneau, N. Galie, et al. 2002. Inhaled iloprost for severe pulmonary hypertension. N. Engl. J. Med. 347:322-329.
18. Seeger, W., D. Walmrath, F. Grimminger, et al. 1994. Adult respiratory distress syndrome: model systems using isolated perfused rabbit lungs. Methods Enzymol. 233:549-584.
19. Schermuly, R.T., A. Roehl, N. Weissmann, et al. 2000. Subthreshold doses of specific phosphodiesterase type 3 and 4 inhibitors enhance the pulmonary vasodilatory response to nebulized prostacyclin with improvement in gas exchange. J. Pharmacol. Exp. Ther. 292:512-520.
20. Schmehl, T., J. Gebhart, H. Schutte, et al. 1996. Online laser-photometric monitoring of aerosol deposition in ventilated rabbit lungs. J. Appl. Physiol. 80:351-356.
21. Hildebrand, M., B. Nieuweboer, H. Biere, et al. 1990. Development, validation and practical use of a sensitive and specific radioimmunoassay for the determination of iloprost. Eicosanoids 3:165-169.
22. Rimar, S., and C.N. Gillis. 1993. Selective pulmonary vasodilation by inhaled nitric oxide is due to hemoglobin inactivation. Circulation 88:2884-2887.
23. Lindeborg, D.M., B.P. Kavanagh, K. Van Meurs, et al. 1995. Inhaled nitric oxide does not alter the longitudinal distribution of pulmonary vascular resistance. J. Appl. Physiol. 78:341-348.
24. Rimar, S., and C.N. Gillis. 1995. Site of pulmonary vasodilation by inhaled nitric oxide in the perfused lung. J. Appl. Physiol. 78:1745-1749.
25. Walmrath, D., R. Schermuly, J. Pilch, et al. 1997. Effects of inhaled versus intravenous vasodilators in experimental pulmonary hypertension. Eur. Respir. J. 10:1084-1092.
26. Krause, W., M. Humpel, and G.A. Hoyer. 1984. Biotransformation of the stable prostacyclin analogue, iloprost, in the rat. Drug Metab. Dispos. 12:645-651.
27. Schermuly, R.T., A. Schulz, H.A. Ghofrani, et al. 2002. Pharmacokinetics and metabolism of infused versus inhaled iloprost in isolated rabbit lungs. J. Pharmacol. Exp. Ther. 303:741-745.
28. Olschewski, H., B. Rohde, J. Behr, et al. 2000. Comparison of inhalation of the prostacyclin analogue iloprost using different nebulizer systems in patients suffering from pulmonary hypertension. Chest 118:1365.
29. Iwamoto, J., and F.C. Morin, III. 1993. Nitric oxide inhibition varies with hemoglobin saturation. J. Appl. Physiol. 75:2332-2336.
30. Tod, M.L., D.C. O'Donnel, and J.B. Gordon. 1995. Sites of inhaled NO-induced vasodilation during hypoxia and U-46619 infusion in isolated lamb lungs. Am. J. Physiol. 268:H1422-H1427.
31. Fishman, A.P. 1976. Hypoxia on the pulmonary circulation. How and where it acts. Circ. Res. 38:221-231.
32. + channels in resistance pulmonary arteries explains regional heterogeneity in hypoxic pulmonary vasoconstriction: ionic diversity in smooth muscle cells. Circ. Res. 95:308-318.
33. Roseman, T.J., and S.H. Yalkowsky. 1973. Physicochemical properties of prostaglandin F2 alpha (tromethamine salt): solubility behavior, surface properties, and ionization constants. J. Pharm. Sci. 62:1680-1685.
34. Bito, L.Z., and R.A. Baroody. 1975. Impermeability of rabbit erythrocytes to prostaglandins. Am. J. Physiol. 229:1580-1584.
35. Anderson, M.W., and T.E. Eling. 1976. Prostaglandin removal and metabolism by isolated perfused rat lung. Prostaglandins 11:645-677.
36. Eling, T.E., H.J. Hawkins, and M.W. Anderson. 1977. Structural requirements for, and the effects of chemicals on, the rat pulmonary inactivation of prostaglandins. Prostaglandins 14:51-60.
37. Eling, I.E., and M.W. Anderson. 1976. Studies on the biosynthesis, metabolism and transport of prostaglandins by the lung. Agents Actions 6:543-546.
38. Kanai, N., R. Lu, J.A. Satriano, et al. 1995. Identification and characterization of a prostaglandin transporter. Science 268:866-869.
39. Lu, R., N. Kanai, Y. Bao, et al. 1996. Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA(hPGT). J. Clin. Invest. 98:1142-1149.
40. Ghofrani, H.A., M.G. Kohstall, N. Weissmann, et al. 2001. Alveolar epithelial barrier functions in ventilated perfused rabbit lungs. Am. J. Physiol. Lung Cell Mol. Physiol 280:L896-L904.
41. 2alpha) receptor-dependent regulation of prostaglandin transport. Mol. Pharmacol. 59:1506-1513.
42. Funk, C.D., L. Furci, G.A. FitzGerald, et al. 1993. Cloning and expression of a cDNA for the human prostaglandin E receptor EP1 subtype. J. Biol. Chem. 268:26767-26772.
43. Breyer, R.M., C.K. Bagdassarian, S.A. Myers, et al. 2001. Prostanoid receptors: subtypes and signaling. Annu. Rev. Pharmacol. Toxicol. 41:661-690.
44. Archer, S.L., D. Mike, J. Crow, et al. 1996. A placebo-controlled trial of prostacyclin in acute respiratory failure in COPD. Chest 109:750-755.
45. Zucker, T.P., D. Bonisch, A. Hasse, et al. 1998. Tolerance development to antimitogenic actions of prostacyclin but not of prostaglandin El in coronary artery smooth muscle cells. Eur. J. Pharmacol. 345:213-220.
46. Fisch, A., K. Tobusch, K. Veit, et al. 1997. Prostacyclin receptor desensitization is a reversible phenomenon in human platelets. Circulation 96:756-760.
47. Nilius, S.M., A. Hasse, P. Kuger, et al. 2000. Agonist-induced long-term desensitization of the human prostacyclin receptor. FEBS Lett. 484:211-216.
48. Smyth, E.M., P.V. Nestor, and G.A. FitzGerald. 1996. Agonist-dependent phosphorylation of an epitope-tagged human prostacyclin receptor. J. Biol. Chem. 271:33698-33704.