title: Indinavir crystallization around the loop of Henle: experimental evidence.
abstract: OBJECTIVE
  To determine the probable site of the nephron and the plasma indinavir (IDV) concentration at which intrarenal IDV crystallization occurs.
  
  
  METHODS
  We performed in vitro crystallization experiments in IDV solutions simulating conditions found in the nephron.
  
  
  METHODS
  To determine intrarenal IDV concentrations at which conditions in the nephron allow crystallization, several concentrations of IDV basic solutions (0-800 mM) were titrated from pH 4.0 to higher pH values until crystals formed within 1 minute. Based on the combination of pH and ionic strength at which crystals formed, we determined the site of the nephron at which this combination was first attained. Based on the capacity for concentration at that site, we were able to measure the corresponding plasma IDV concentration.
  
  
  RESULTS
  Under conditions normally found at the proximal tubule (i.e., pH 6.7 and ionic strength of 200 mM), IDV crystallized at 200 mg/L. Under conditions applying to the loop of Henle, pH 7.4 and ionic strength of 200 mM, IDV crystallized at 125 mg/L, which would correspond to a plasma IDV concentration of 8 mg/L.
  
  
  CONCLUSIONS
  IDV crystallization is most likely in the loop of Henle and may already start at plasma IDV concentrations as low as 8 mg/L. Increasing hydration does not reduce the risk of IDV crystallization in the loop of Henle but instead prevents IDV crystallization and aggregation in the lower urinary tract. It remains to be confirmed whether prevention of high IDV plasma concentrations will reduce the risk of IDV crystallization in the loop of Henle.
authors.affiliation: Pharmaco-Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus University Medical Center (EMCR), Rotterdam, The Netherlands.
authors.forename: J P
authors.initials: JP
authors.lastname: Dieleman
authors.forename: S
authors.initials: S
authors.lastname: Salahuddin
authors.forename: Y S
authors.initials: YS
authors.lastname: Hsu
authors.forename: D M
authors.initials: DM
authors.lastname: Burger
authors.forename: I C
authors.initials: IC
authors.lastname: Gyssens
authors.forename: M C
authors.initials: MC
authors.lastname: Sturkenboom
authors.forename: B H
authors.initials: BH
authors.lastname: Stricker
authors.forename: D J
authors.initials: DJ
authors.lastname: Kok
mesh_terms: D003460:Crystallization; D017320:HIV Protease Inhibitors / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019469:Indinavir / Q000737:chemistry*; D008138:Loop of Henle / Q000737:chemistry*; D012995:Solubility
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir