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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 11/2015

01-11-2015 | Case Report

Pharmacokinetics and Tolerability of Intravenous Sildenafil in Two Subjects with Child–Turcotte–Pugh Class C Cirrhosis and Renal Dysfunction

Authors: Ayse L. Mindikoglu, Thomas C. Dowling, David J. Schaub, William R. Hutson, Darryn R. Potosky, Robert H. Christenson, Rolf N. Barth, John C. LaMattina, Steven I. Hanish, Matthew R. Weir, Jean-Pierre Raufman

Published in: Digestive Diseases and Sciences | Issue 11/2015

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Excerpt

Phosphodiesterase-5 (PDE-5) inhibitors play an important role in the treatment of complications of cirrhosis. They have been used successfully to treat portopulmonary hypertension (PPHTN) [1‐4], a complication in 5 % of subjects with cirrhosis [5]. Additionally, previous studies showed that PDE-5 inhibitors reduced portal pressures and hepatic venous pressure gradients, thereby improving hemodynamics in cirrhosis [6‐8]. Moreover, in cirrhotic rats, PDE-5 inhibitors increased fractional excretion of Na, reduced plasma renin levels, and improved renal blood flow and glomerular filtration rate [9]. …
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Hemnes AR, Champion HC. Sildenafil, a PDE5 inhibitor, in the treatment of pulmonary hypertension. Expert Rev Cardiovasc Ther. 2006;4:293–300.CrossRefPubMed
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Gough MS, White RJ. Sildenafil therapy is associated with improved hemodynamics in liver transplantation candidates with pulmonary arterial hypertension. Liver Transpl. 2009;15:30–36.CrossRefPubMed
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Krowka MJ, Swanson KL, Frantz RP, et al. Portopulmonary hypertension: results from a 10-year screening algorithm. Hepatology. 2006;44:1502–1510.CrossRefPubMed
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Deibert P, Schumacher YO, Ruecker G, et al. Effect of vardenafil, an inhibitor of phosphodiesterase-5, on portal haemodynamics in normal and cirrhotic liver—results of a pilot study. Aliment Pharmacol Ther. 2006;23:121–128.CrossRefPubMed
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Halverscheid L, Deibert P, Schmidt R, et al. Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the liver. BMC Gastroenterol. 2009;9:69.PubMedCentralCrossRefPubMed
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Tahseldar-Roumieh R, Ghali-Ghoul R, Lugnier C, et al. Effect of phosphodiesterase 5 inhibitor on alteration in vascular smooth muscle sensitivity and renal function in rats with liver cirrhosis. Am J Physiol Heart Circ Physiol. 2006;290:H481–H488.CrossRefPubMed
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Thiesson HC, Jensen BL, Jespersen B, et al. Inhibition of cGMP-specific phosphodiesterase type 5 reduces sodium excretion and arterial blood pressure in patients with NaCl retention and ascites. Am J Physiol Renal Physiol. 2005;288:F1044–F1052.CrossRefPubMed
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Muirhead GJ, Wilner K, Colburn W, et al. The effects of age and renal and hepatic impairment on the pharmacokinetics of sildenafil. Br J Clin Pharmacol. 2002;53:21S–30S.PubMedCentralCrossRefPubMed
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Nichols DJ, Muirhead GJ, Harness JA. Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: absolute bioavailability, food effects and dose proportionality. Br J Clin Pharmacol. 2002;53:5S–12S.PubMedCentralCrossRefPubMed
Metadata
Title
Pharmacokinetics and Tolerability of Intravenous Sildenafil in Two Subjects with Child–Turcotte–Pugh Class C Cirrhosis and Renal Dysfunction
Authors
Ayse L. Mindikoglu
Thomas C. Dowling
David J. Schaub
William R. Hutson
Darryn R. Potosky
Robert H. Christenson
Rolf N. Barth
John C. LaMattina
Steven I. Hanish
Matthew R. Weir
Jean-Pierre Raufman
Publication date
01-11-2015
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 11/2015
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-015-3771-0

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