title: The extra-phosphate intestinal load from medications: is it a real concern?
abstract: OBJECTIVE
  Reduction of intestinal load of phosphorus is important for the prevention and treatment of chronic kidney disease (CKD)-mineral and bone disorder (MBD). However, this strategy is limited by patients' poor adherence to dietary prescription and by the existence of hidden sources of phosphorus. In addition to food containing phosphate-based additives, it was recently claimed that medications may contribute to increase the load of phosphate (P), mainly present as an excipient. To identify medications containing P as an excipient, we performed a systematic screening of medications which could potentially be prescribed for chronic oral therapies in CKD patients.
  
  
  METHODS
  We examined 311 active pharmaceutical ingredients (APIs) and 3763 branded or generic medications, identified by the anatomical therapeutic chemical (ATC) international classification system.
  
  
  RESULTS
  Sixty APIs (19.3 %) included at least one medication containing P as an excipient. In total, 472 medications (12.5 %) listed P as an excipient. The prevalence of medications containing phosphate as an excipient was highest for oral antidiabetic medications (23.8 %), followed by antidepressant (19.2 %), antihypertensive (17.5 %) and gastro-intestinal tract (16.4 %) medications. All other classes showed a prevalence <10 %. Within each ATC class, the APIs at risk of containing phosphate were identified as well as the prevalence of both branded and generic medications. Calcium hydrogen phosphate was the most prevalent form (77.7 %) of phosphate as an excipient.
  
  
  CONCLUSIONS
  Our results suggest that the prevalence of phosphate-containing medications is quite low and it is possible to identify, within each drug category, the medications containing P as an excipient. Calcium phosphate, the most prevalent form, has a lower rate of intestinal absorption than sodium phosphate salts. We did not measure the actual P content, but existing data (measured or estimated) show that it is generally low, except for a few medications that can be easily identified. Thus, the extra-phosphate load from medications may be of concern only in special cases, which could be further limited when correct information and prescriptions are given. The extra-phosphate load from P-containing food and beverages remains the main concern of hidden phosphorus sources in CKD patients.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy. adamasco.cupisti@med.unipi.it.
authors.forename: Adamasco
authors.initials: A
authors.lastname: Cupisti
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Moriconi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: D'Alessandro
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Verde
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Marchini
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Saba
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy.
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Egidi
mesh_terms: D000284:Administration, Oral; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D004339:Drug Compounding; D005079:Excipients / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000032:analysis* / Q000378:metabolism; D010710:Phosphates / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis* / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D005079:Excipients; D004364:Pharmaceutical Preparations; D010710:Phosphates
keywords: CKD; Drug; Excipient; Medication; Phosphate