title: Chloroquine reduces the bioavailability of methotrexate in patients with rheumatoid arthritis. A possible mechanism of reduced hepatotoxicity.
abstract: OBJECTIVE
  To evaluate the effects of a single dose of chloroquine (CQ) on the pharmacokinetics of methotrexate (MTX) in patients with rheumatoid arthritis.
  
  
  METHODS
  Eleven patients (ages 41-75 years) who were taking oral doses of MTX (15 mg/week) were studied after a dose of MTX alone and after a dose of MTX plus CQ (250 mg). Plasma and urine samples were collected for 24 hours after dose intake, and the concentrations of MTX and its major metabolite 7-hydroxymethotrexate were determined by high-performance liquid chromatography.
  
  
  RESULTS
  Administration of CQ together with MTX caused a reduction in the area under the plasma MTX concentration versus time curve (AUC). The median value of individual AUC ratios (MTX/MTX + CQ) was 1.6 (95% confidence interval 1.2-3.6).
  
  
  CONCLUSIONS
  The most likely mechanism for the interaction is that CQ reduces the bioavailability of MTX. This gives a possible explanation for a suggested reduction in MTX-associated liver toxicity by coadministration of CQ. The significance of the interaction for the therapeutic effect remains to be elucidated.
authors.affiliation: Danderyd Hospital, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Seideman
authors.forename: F
authors.initials: F
authors.lastname: Albertioni
authors.forename: O
authors.initials: O
authors.lastname: Beck
authors.forename: S
authors.initials: S
authors.lastname: Eksborg
authors.forename: C
authors.initials: C
authors.lastname: Peterson
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D001682:Biological Availability; D002738:Chloroquine / Q000008:administration & dosage*; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008875:Middle Aged
chemical_list: D002738:Chloroquine; D008727:Methotrexate