Comparative Pharmacokinetic, Pharmacodynamic, Safety, and Tolerability Profiles of 3 Different Formulations of Epoprostenol Sodium for Injection in Healthy Men

Clinical Therapeutics

Volumn 35, Issue 4, 2013, Pages 440-449

  Nicolas, Laurent B ^a   Gutierrez, Marcelo M ^a   Dingemanse, Jasper ^a  

^a ACTELION PHARMACEUTICALS LTD   (Switzerland)

Author keywords

Bioequivalence; Epoprostenol; Hemodynamics; Pharmacokinetic profile; Prostacyclin

Indexed keywords

6 KETO PROSTACYCLIN F1ALPHA; 6,15 DIKETO 13,14 DIHYDRO PROSTACYCLIN F1APHA; ARGININE; DRUG METABOLITE; EPOPROSTENOL ARGININE MANNITOL; EPOPROSTENOL ARGININE SUCROSE; EPOPROSTENOL GLYCINE MANNITOL; GLYCINE; MANNITOL; PROSTACYCLIN; UNCLASSIFIED DRUG;

ADULT; ARTICLE; BIOEQUIVALENCE; BLOOD SAMPLING; CLINICAL ARTICLE; CONCENTRATION RESPONSE; CROSSOVER PROCEDURE; DIASTOLIC BLOOD PRESSURE; DRUG BLOOD LEVEL; DRUG FORMULATION; DRUG SAFETY; DRUG TOLERABILITY; ECHOCARDIOGRAPHY; HEART INDEX; HEART OUTPUT; HEART RATE; HUMAN; MALE; MEAN ARTERIAL PRESSURE; NORMAL HUMAN; OPEN STUDY; PROSPECTIVE STUDY; SYSTOLIC BLOOD PRESSURE;

ANTIHYPERTENSIVE AGENTS; AREA UNDER CURVE; CROSS-OVER STUDIES; EPOPROSTENOL; HUMANS; MALE; PROSPECTIVE STUDIES; REFERENCE VALUES;

EID: 84876341311     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2013.02.013     Document Type: Article

References (20)

1. Farber H.W., Loscalzo J. Pulmonary arterial hypertension. N Engl J Med 2004, 351:1655-1665.
2. Schannwell C.M., Steiner S., Strauer B.E. Diagnostics in pulmonary hypertension. J Physiol Pharmacol 2007, 58(Suppl 5):591-602.
3. Barst R.J., Rubin L.J., Long W.A., et al. The Primary Pulmonary Hypertension Study Group. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med 1996, 334:296-302.
4. Bresser P., Fedullo P.F., Auger W.R., et al. Continuous intravenous epoprostenol for chronic thromboembolic pulmonary hypertension. Eur Respir J 2004, 23:595-600.
5. Roeleveld R.J., Vonk-Noordegraaf A., Marcus J.T., et al. Effects of epoprostenol on right ventricular hypertrophy and dilatation in pulmonary hypertension. Chest 2004, 125:572-579.
6. Naeije R., Huez S. Expert opinion on available options treating pulmonary arterial hypertension. Expert Opin Pharmacother 2007, 8:2247-2265.
7. Flolan [prescribing information] January 2008, Accessed February 28, 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020444s016lbl.pdf.
8. Veletri [prescribing information] 2011, Accessed February 28, 2013. http://www.veletri.com/pdf/veletri_full_prescribing_information.pdf.
9. Lambert O., Bandilla D., Iyer R., Witchey-Lakshmanan L., Palepu N. Stability and microbiological properties of a new formulation of epoprostenol sodium when reconstituted and diluted. Drug Des Devel Ther 2012, 6:61-70.
10. Chaumais M.C., Jobard M., Huertas A., et al. Pharmacokinetic evaluation of continuous intravenous epoprostenol. Expert Opin Drug Metab Toxicol 2010, 6:1587-1598.
11. Nicolas L.B., Krause A., Gutierrez M.M., Dingemanse J. Integrated pharmacokinetics and pharmacodynamics of epoprostenol in healthy subjects. Br J Clin Pharmacol 2012, 74:978-989.
12. Enzler M., Schipp S., Nicolas L.B., Dingemanse J., Siethoff C. Determination of 6-keto prostaglandin F1alpha and its metabolites in human plasma by LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 2012, 901:67-71.
13. Lambert O., Bandilla D. Stability and preservation of a new formulation of epoprostenol sodium for treatment of pulmonary arterial hypertension. Drug Des Devel Ther 2012, 6:235-244.
14. Guidance for Industry: Bioavailability and Bioequivalence Studies for Orally Administered Drug Products-General Considerations 2001, US Food and Drug Administration, US Food and Drug Administration, Silver Spring, Md.
15. Rich S., McLaughlin V.V. The effects of chronic prostacyclin therapy on cardiac output and symptoms in primary pulmonary hypertension. J Am Coll Cardiol 1999, 34:1184-1187.
16. Humbert M., Sitbon O., Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med 2004, 351:1425-1436.
17. Hlebowicz J., Lindstedt S., Bjorgell O., Dencker M. Relationship between postprandial changes in cardiac left ventricular function, glucose and insulin concentrations, gastric emptying, and satiety in healthy subjects. Nutr J 2011, 10:26.
18. Ishimine M., Takamoto T., Nitta M., Marumo F., Murakami K., Takasu N. Postprandial hemodynamic changes evaluated by a Doppler echocardiographic method. Jpn Heart J 1994, 35:35-42.
19. Nielsen C.B., Bech J.N., Pedersen E.B. Effects of prostacyclin on renal haemodynamics, renal tubular function and vasoactive hormones in healthy humans: a placebo-controlled dose-response study. Br J Clin Pharmacol 1997, 44:471-476.
20. Szczeklik J., Szczeklik A., Nizankowski R. Haemodynamic changes induced by prostacyclin in man. Br Heart J 1980, 44:254-258.