title: Quinine pharmacokinetics in chronic haemodialysis patients.
abstract: OBJECTIVE
  Quinine is often used to prevent muscle cramps in patients with chronic renal failure. A standard dose of 300 mg at bedtime is usually recommended, but little is known about the pharmacokinetics of quinine in the presence of renal failure.
  
  
  METHODS
  We studied the pharmacokinetics of quinine in eight normal subjects and eight patients with chronic renal failure on haemodialysis after a single oral dose of quinine sulphate (300 mg).
  
  
  RESULTS
  The concentration of alpha1-acid glycoprotein (AAG), the major binding protein for quinine, was increased in haemodialysis patients compared with control subjects (1.52 g l-1 vs 0.63 g l-1 [mean difference 1.033; 95% CI 0.735, 1.330]) whereas albumin levels were decreased (30 g l-1 vs 40 g l-1 [mean difference 9.5; 95% CI 3.048, 15.952]). Accordingly, the free fraction of quinine was decreased (0.024 vs 0.063 [mean difference 0.0380; 95% CI 0.0221, 0.0539]) and the apparent volume of distribution tended to decrease (0.95 l kg-1 vs 1.43 l kg-1 [mean difference 0.480; 95% CI 0.193, 1.154]). The quinine binding ratio correlated with the plasma concentration of AAG but not that of albumin. The clearance of free (unbound) quinine was increased in haemodialysis patients compared with controls (67.9 ml min-1 kg-1 vs 41.1 ml min-1 kg-1 [mean difference -26.8; 95% CI, -56.994, 3.469]), and the area under the curve (AUC) of the two main metabolites, 3-hydroxyquinine and 10,11-dihydroxydihydroquinine were increased.
  
  
  CONCLUSIONS
  In patients with chronic renal failure, there is an increase in plasma protein binding and in the clearance of free drug, resulting in lower plasma concentration of free quinine.
authors.affiliation: Departments of Medicine and Biochemistry, Centre Hospitalier de l' Université de Montréal, Montréal, Canada.
authors.forename: Louise
authors.initials: L
authors.lastname: Roy
authors.forename: Pierre
authors.initials: P
authors.lastname: Bannon
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Villeneuve
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009125:Muscle Relaxants, Central / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009961:Orosomucoid / Q000032:analysis; D011802:Quinidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011803:Quinine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011809:Quinones / Q000493:pharmacokinetics; D006435:Renal Dialysis
chemical_list: C429827:10,11-dihydroxydihydroquinine; D009125:Muscle Relaxants, Central; D009961:Orosomucoid; D011809:Quinones; C013569:3-hydroxyquinidine; D011803:Quinine; D011802:Quinidine