The Effect of sildenafil on gastric emptying in patients with end-stage renal failure and symptoms of Gastroparesis

• Published in: Clinical pharmacology and therapeutics 2004-09, Vol.76 (3), p.281-286
• Main Authors: Dishy, V., Cohen Pour, M., Feldman, L., Naftali, T., Baumer, M., Efrati, S., Golik, A., Horne, T., Weissgarten, J.
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; Digestive system; Female; Gastric Emptying - drug effects; Gastroparesis - physiopathology; Humans; Kidney Failure, Chronic - physiopathology; Male; Medical sciences; Middle Aged; Nitric Oxide - biosynthesis; Pharmacology. Drug treatments; Piperazines - pharmacology; Purines; Sildenafil Citrate; Sulfones
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1016/j.clpt.2004.04.012

Background Delayed gastric emptying is a common disorder among patients with end‐stage renal failure (ESRF). Pyloric relaxation, a major determinant of gastric emptying, is a nitric oxide (NO)–mediated process. NO‐induced smooth muscle relaxation is mediated through its second messenger cyclic guanosine monophosphate, which is broken by tissue phosphodiesterases (PDEs). Thus the inhibition of cyclic guanosine monophosphate breakdown by PDE inhibitors can potentiate NO‐mediated responses and facilitate pyloric relaxation. In an animal model of diabetes mellitus, treatment with sildenafil (a PDE‐5 inhibitor) restored NO‐mediated pyloric relaxation and improved gastric emptying. The aim of our study was to examine the hypothesis that sildenafil may improve gastric emptying in patients with ESRF and symptoms of gastric paresis. Methods We studied 12 patients with ESRF (6 men; age range, 54–80 years; 5 with diabetic nephropathy; 4 ± 1 years receiving long‐term renal replacement therapy) after either placebo or a 25‐mg tablet of sildenafil (Viagra; Pfizer Inc). Gastric emptying of a solid meal (one medium‐sized fried egg mixed with 37 MBq [1 mCi] technetium Tc 99m phytate plus 1 slice of bread and 150 mL of water at the end of the meal) was assessed 1 hour after dosing by use of a single‐headed camera. Images were acquired every 30 seconds for 90 minutes immediately after patients ate. Results The gastric emptying rate was decreased at baseline (after placebo), to 33% ± 6% (normal, ≥50%). Treatment with sildenafil had no effect on gastric emptying rates after 90 minutes (from 33% ± 6% after placebo to 30% ± 6% after sildenafil, P = .9). Conclusions Sildenafil did not improve gastric emptying in patients with ESRF and gastric paresis. Sildenafil may have opposing effects on gastric peristalsis (causing gastric relaxation) compared with its effects on pyloric relaxation. Studies combining sildenafil with prokinetic drugs are of interest. Clinical Pharmacology & Therapeutics (2004) 76, 281–286; doi: 10.1016/j.clpt.2004.04.012