title: Pharmacokinetic interaction between sorafenib and prednisolone in a patient with hepatocellular carcinoma.
abstract: OBJECTIVE
  Sorafenib is primarily metabolized in the liver, by CYP3A4-mediated oxidation and UGT1A9-mediated glucuronidation. However, there is little information about the pharmacokinetic interaction of sorafenib. Here, we report a pharmacokinetic interaction between sorafenib and the CYP3A4 inducer prednisolone in a patient with hepatocellular carcinoma (HCC).
  
  
  METHODS
  The patient was a 72-year-old woman diagnosed with HCC. She was treated with sorafenib at 400 mg daily. On day 9, sorafenib was discontinued due to drug eruption. Nine months later, she was rechallenged with sorafenib at 400 mg daily concurrently with oral prednisolone. Prednisolone was started at 20 mg daily and was tapered by 5 mg every 14 days. We assessed the pharmacokinetics of sorafenib and its major metabolite M-2.
  
  
  RESULTS
  The concentration of sorafenib was gradually increased following tapering of prednisolone. On day 56 after rechallenge, she developed G3 oral mucositis. At this time, serum trough concentrations of sorafenib and M-2 were at 5.9 and 1.1 μg/ml, respectively. Consequently, sorafenib dosage was reduced to 200 mg daily, and the oral mucositis was attenuated. The subsequent concentrations of sorafenib and M-2 obtained with a dose of 200 mg daily ranged from 1 to 3 μg/ml and from 0.1 to 0.4 μg/ml, respectively. Computed tomography scan showed a complete response of the liver tumor with no further recurrence of the rash.
  
  
  CONCLUSIONS
  We have demonstrated for the first time that prednisolone stimulates the sorafenib metabolism and that therapeutic drug monitoring could be useful during sorafenib therapy.
authors.affiliation: Department of Pharmacy, Shiga University of Medical Science Hospital, Seta Tsukinowacho, Otsu City, Shiga, 520-2192, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Noda
authors.forename: Makoto
authors.initials: M
authors.lastname: Shioya
authors.forename: Daiki
authors.initials: D
authors.lastname: Hira
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujiyama
authors.forename: Shin-ya
authors.initials: SY
authors.lastname: Morita
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Terada
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D001711:Biotransformation / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D003875:Drug Eruptions; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D011239:Prednisolone / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077157:Sorafenib; D013280:Stomatitis / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D010671:Phenylurea Compounds; D009536:Niacinamide; D011239:Prednisolone; D000077157:Sorafenib