ABSTRACT
Hyperphosphatemia, a common complication in patients with end-stage renal disease, is treated with oral phosphate-binding medications that restrict phosphorus absorption from the gastrointestinal (GI) tract. Impaired product performance, such as failure to disintegrate and/or dissolve in the GI tract, could limit the efficacy of the phosphate binder. Disintegration may be as important as dissolution for predicting in vitro product performance for medications that act locally on the GI tract, such as phosphate binders. Furthermore, patients with end-stage renal disease have a wide range in GI pH, and pH can influence a product's performance. The purpose of this study was to determine the effect of pH on in vitro disintegration of phosphate binders. Fifteen different commercially available phosphate binders (seven calcium carbonate tablet formulations, two calcium acetate tablet formulations, three aluminum hydroxide capsule formulations, and three aluminum hydroxide tablet formulations) were studied using the United States Pharmacopeia (USP) standard disintegration apparatus. Phosphate binders were tested in simulated gastric fluid (pH 1.5), distilled water (pH 5.1), and simulated intestinal fluid (pH 7.5). Product failure was defined as two or more individual tablets or capsules failing to disintegrate completely within 30 minutes. Results indicate that 9 of the 15 phosphate binders tested showed statistically significant differences in disintegration time (DT) based on pH. The percentage of binders that passed the disintegration study test in distilled water, gastric fluid, and intestinal fluid were 80%, 80%, and 73%, respectively. The findings of this study show that the disintegration of commercially available phosphate binders is highly variable. The pH significantly affected in vitro disintegration in the majority of phosphate binders tested; how significantly this affects in vivo performance has yet to be studied.
Subject(s)
Acetates/chemistry , Aluminum Hydroxide/chemistry , Antacids/chemistry , Calcium Carbonate/chemistry , Calcium/chemistry , Gastric Juice/chemistry , Absorption , Acetates/therapeutic use , Administration, Oral , Aluminum Hydroxide/therapeutic use , Antacids/therapeutic use , Calcium/therapeutic use , Calcium Carbonate/therapeutic use , Capsules , Chemistry, Pharmaceutical , Forecasting , Gastric Mucosa/metabolism , Humans , Hydrogen-Ion Concentration , Intestinal Absorption/drug effects , Intestinal Secretions/chemistry , Kidney Failure, Chronic/complications , Phosphates/blood , Phosphates/chemistry , Phosphates/metabolism , Solubility , Tablets , Time Factors , Water/chemistryABSTRACT
A 7-year-old boy with asthma was receiving the leukotriene receptor antagonist pranlukast (Ultair; SmithKline Beecham; Pittsburgh) as part of an open-label clinical trial. The patient's asthma improved, and he remained asymptomatic; but routine study evaluations 9 to 12 months into therapy showed microhematuria, proteinuria, glucosuria, anemia, and renal insufficiency. Renal biopsy demonstrated changes classic for acute allergic tubulointerstitial nephritis (ATIN), with mixed interstitial inflammatory infiltrate including eosinophils. Within 6 months of pranlukast withdrawal, anemia resolved and urinary sediment and renal function normalized. The case demonstrates that hypersensitivity reaction to pranlukast and resultant ATIN is possible, and that periodic urine testing in patients receiving pranlukast should be considered.
