Pharmacokinetic optimisation of the treatment of peptic ulcer in patients with renal failure.
The pathogenesis of peptic ulceration is not yet clear. It could be due to an imbalance between acid secretion and mucosal defensive and/or protective mechanisms, but the association between Helicobacter pylori and peptic ulceration has questioned this hypothesis. Therefore, drugs inhibiting acid secretion and/or eradicating H. pylori are of major interest. Peptic ulcer disease is often associated with renal failure. For the selection of the proper dosage of these agents their pharmacokinetic properties and alterations in pharmacokinetics in various disease states, including renal failure, should be known. As histamine H2-receptor antagonists and pirenzepine are mainly eliminated by the renal route their elimination is dependent on creatinine clearance. Consequently, their elimination will be impaired in patients with renal insufficiency, which makes dosage reduction mandatory in these patients. No dosage supplementation is necessary after any type of dialysis because the drugs are removed in insignificant amounts by the various blood purification procedures. Misoprostol and proton pump inhibitors, such as omeprazole, lansoprazole and pantoprazole, are primarily eliminated by nonrenal routes. Therefore no dosage adjustments are necessary in patients with renal insufficiency. Bismuth salts, sucralfate and antacids should be avoided in patients with renal failure because of the accumulation of their cations and the associated risk of toxic reactions. For most agents more long term experience from comparative and double-blinded studies is needed to define better their clinical efficacy and tolerability in patients with renal failure.
Department of Internal Medicine II, Technical University, Aachen, Germany.
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Gladziwa
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Koltz
D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics; D001682:Biological Availability; D006207:Half-Life; D006635:Histamine H2 Antagonists / Q000493:pharmacokinetics*; D006801:Humans; D008657:Metabolic Clearance Rate; D010437:Peptic Ulcer / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology; D017494:Proton Pumps / Q000378:metabolism; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism
D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D017494:Proton Pumps