Pharmacokinetics and Tolerability of Intravenous Sildenafil in Two Subjects with Child–Turcotte–Pugh Class C Cirrhosis and Renal Dysfunction
| Autor: | Thomas C. Dowling, Steven I. Hanish, Robert H. Christenson, David J. Schaub, John C. LaMattina, Matthew R. Weir, Ayse L. Mindikoglu, William R. Hutson, Rolf N. Barth, Jean-Pierre Raufman, Darryn Potosky |
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| Rok vydání: | 2015 |
| Předmět: |
Liver Cirrhosis
Male medicine.medical_specialty Cirrhosis Physiology Sildenafil Renal function Kidney Severity of Illness Index Gastroenterology Sildenafil Citrate Article chemistry.chemical_compound Pharmacokinetics Internal medicine Ascites medicine Humans business.industry Middle Aged Phosphodiesterase 5 Inhibitors medicine.disease Treatment Outcome medicine.anatomical_structure Tolerability chemistry Anesthesia Injections Intravenous Portal hypertension Kidney Diseases Drug Monitoring medicine.symptom business Glomerular Filtration Rate |
| Zdroj: | Digestive Diseases and Sciences. 60:3491-3494 |
| ISSN: | 1573-2568 0163-2116 |
| Popis: | Phosphodiesterase-5 (PDE-5) inhibitors have been used successfully in patients with cirrhosis to treat porto-pulmonary hypertension. Additionally, in cirrhosis, PDE-5 inhibitors can potentially improve portal hypertension and renal hemodynamics. No pharmacokinetics and tolerability studies of intravenous (IV) sildenafil have been conducted in Child-Turcotte-Pugh (CTP) class C cirrhosis and renal dysfunction. We report two subjects with CTP class C cirrhosis and estimated glomerular filtration rate of 25.8 and 22.4 ml/min/1.73m2 treated with a single-dose, IV bolus injection of 2.5 mg sildenafil. Both subjects had diuretic-refractory ascites with model for end-stage liver disease scores of 25 and 35. Both subjects tolerated IV Sildenafil without side effects. The observed maximum concentrations of plasma sildenafil were 35 and 20.6 ng/ml, with modeled pharmacokinetic estimates for clearance (11.9 and 14.9 L/hr), volumes of distribution (72.8 and 77.3 L) and half-life (4.2 and 3.6 hrs). N-desmethyl sildenafil concentrations ranged from 3 to 40% of the parent concentrations. Our results showed that in CTP class C cirrhosis and renal dysfunction, IV bolus injection of 2.5 mg sildenafil is safe and tolerable. |
| Databáze: | OpenAIRE |
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