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  • Title: Pharmacokinetics and pharmacodynamics of H2-receptor antagonists in patients with renal insufficiency.
    Author: Gladziwa U, Klotz U.
    Journal: Clin Pharmacokinet; 1993 Apr; 24(4):319-32. PubMed ID: 8098275.
    Abstract:
    H2-receptor antagonists are frequently used in patients with renal insufficiency to treat hyperacidity and resultant peptic ulceration. All H2-antagonists are mainly eliminated by the renal route (glomerular filtration and tubular secretion). Since it is dependent on creatinine clearance (CLCR), elimination will be impaired in renal insufficiency. Protein binding and volumes of distribution (Vd) of H2-antagonists are not significantly altered in patients with renal impairment. Bioavailability (F) is similar in patients with and without renal insufficiency, except for nizatidine, which has an F that is lower in uraemic patients. When given in similar doses, mean peak concentrations (Cmax) and area under the concentration-time curve (AUC) are higher in patients with renal insufficiency than in those with normal renal function. Thus, maintenance doses of H2-antagonists should be reduced in line with reductions in CLCR. The time to reach Cmax is similar for all drugs except ranitidine, which has a delayed Cmax. Due to the decreased renal clearance (CLR), elimination half-life (t1/2) is prolonged 3- to 8-fold depending upon the degree of renal failure and the particular drug. H2-antagonists are removed by various dialysis procedures in insignificant amounts. Thus, no dosage supplementation is necessary after any type of dialysis therapy. By means of intragastric long term pH-metry it has been shown that inhibition of gastric acid secretion is prolonged in patients with renal insufficiency.
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