title: Effects of imatinib mesylate on the pharmacokinetics of paracetamol (acetaminophen) in Korean patients with chronic myelogenous leukaemia.
abstract: OBJECTIVE
  The major objective of the present study was to investigate the effect of imatinib on the pharmacokinetics of paracetamol in patients with chronic myelogenous leukaemia (CML).
  
  
  METHODS
  Patients (n = 12) received a single oral dose of acetaminophen 1000 mg on day 1 (control). On days 2-8, imatinib 400 mg was administered daily. On day 8 (treatment), another 1000 mg dose of paracetamol was administered 1 h after the morning dose of imatinib 400 mg. Blood and urine samples were collected for bioanalytical analyses.
  
  
  RESULTS
  The area under the plasma concentration-time curve (AUC) for paracetamol, paracetamol glucuronide and paracetamol sulphate under control conditions was similar to that after treatment with imatinib; the 90% confidence interval of the log AUC ratio was within 0.8 to 1.25. Urinary excretion of paracetamol, paracetamol glucuronide and paracetamol sulphate was also unaffected by imatinib. The pharmacokinetics of paracetamol and imatinib in Korean patients with CML were similar to previous pharmacokinetic results in white patients with CML. Co-administration of a single dose of paracetamol and multiple doses of imatinib was well tolerated and safety profiles were similar to those of either drug alone.
  
  
  CONCLUSIONS
  The pharmacokinetics of paracetamol and its major metabolites in the presence of imatinib were similar to those of the control conditions and the combination was well tolerated. These findings suggest that imatinib can be safely administered with paracetamol without dose adjustment of either drug.
authors.affiliation: Division of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. dwkim@catholic.ac.kr
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Eugene Y
authors.initials: EY
authors.lastname: Tan
authors.forename: Yu
authors.initials: Y
authors.lastname: Jin
authors.forename: Sahee
authors.initials: S
authors.lastname: Park
authors.forename: Michael
authors.initials: M
authors.lastname: Hayes
authors.forename: Eren
authors.initials: E
authors.lastname: Demirhan
authors.forename: Horst
authors.initials: H
authors.lastname: Schran
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001549:Benzamides; D004334:Drug Administration Schedule; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006207:Half-Life; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D018712:Analgesics, Non-Narcotic; D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000082:Acetaminophen; D000068877:Imatinib Mesylate