Pharmacokinetic interaction between sorafenib and prednisolone in a patient with hepatocellular carcinoma

Cancer Chemother Pharmacol. 2013 Jul;72(1):269-72. doi: 10.1007/s00280-013-2187-9. Epub 2013 May 15.

Abstract

Purpose: 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).

Patients and 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / blood
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biotransformation / drug effects
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Drug Eruptions
  • Drug Interactions
  • Drug Monitoring
  • Female
  • Humans
  • Liver Neoplasms / blood
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives*
  • Niacinamide / blood
  • Niacinamide / pharmacokinetics
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / adverse effects*
  • Phenylurea Compounds / blood
  • Phenylurea Compounds / pharmacokinetics
  • Phenylurea Compounds / therapeutic use
  • Prednisolone / adverse effects*
  • Prednisolone / pharmacokinetics
  • Prednisolone / therapeutic use
  • Sorafenib
  • Stomatitis / chemically induced
  • Treatment Outcome

Substances

  • Phenylurea Compounds
  • Niacinamide
  • Prednisolone
  • Sorafenib