title: Aluminum toxicokinetics in peritoneal dialysis patients.
abstract: BACKGROUND
  Despite the risk of aluminum (Al) toxicity in dialysis patients, little is known about its toxicokinetics (TK) in this population. A national contamination of dialysate solutions with Al provided the opportunity to study Al TK in peritoneal dialysis (PD) patients and to better understand the influence of covariates on its disposition.
  
  
  METHODS
  Al levels in serum and dialysate as well as other laboratory values were collected prospectively from 83 PD patients after correction of Al contamination. Population TK analyses were conducted with NONMEM VI using standard model discrimination criteria. Covariate analyses were also performed using stepwise forward regression followed by backward deletion.
  
  
  RESULTS
  After correction of Al exposure, serum levels declined in a biphasic manner, which was captured by the TK model. The TK of Al were best described by a 2-compartment model with linear elimination. Total creatinine clearance was a significant covariate for total clearance (CL). Mean parameter estimates for volume of central compartment (V1), CL, volume of peripheral compartment (V2), volume of distribution at steady-state (Vss), and intercompartmental clearance (Q) were 168 L, 8.99 L/day, 12 000 L, 12 168 L, and 4.93 L/day, respectively. Inter-individual variability for CL and V2 were 22.6 and 51.1%, respectively. Al distributional half-life was 8.5 days, while the terminal elimination half-life was 7.2 years. This model confirms that the large Vss reflects the widespread distribution of Al in bone, lungs, liver, and other tissues.
  
  
  CONCLUSIONS
  This study describes the first population Al TK model in a large group of PD patients, which includes a covariate effect. The model confirms the extensive half-life and tissue distribution of Al in a dialysis-dependent population.
authors.affiliation: Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Corinne Seng
authors.initials: CS
authors.lastname: Yue
authors.forename: Megan
authors.initials: M
authors.lastname: Christie
authors.forename: Valery
authors.initials: V
authors.lastname: Lavergne
authors.forename: Tabo
authors.initials: T
authors.lastname: Sikaneta
authors.forename: Hulya
authors.initials: H
authors.lastname: Taskapan
authors.forename: Karine
authors.initials: K
authors.lastname: Mardini
authors.forename: Paul
authors.initials: P
authors.lastname: Tam
authors.forename: Robert
authors.initials: R
authors.lastname: Ting
authors.forename: Marc
authors.initials: M
authors.lastname: Ghannoum
mesh_terms: D000368:Aged; D000535:Aluminum / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D001822:Body Burden; D015314:Dialysis Solutions / Q000493:pharmacokinetics* / Q000633:toxicity*; D004340:Drug Contamination; D005260:Female; D006207:Half-Life; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism / Q000628:therapy*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009864:Ontario; D010530:Peritoneal Dialysis; D011446:Prospective Studies; D011792:Quebec; D018570:Risk Assessment; D012307:Risk Factors; D014018:Tissue Distribution
chemical_list: D015314:Dialysis Solutions; D000535:Aluminum