Associations among regorafenib concentrations, severe adverse reactions, and ABCG2 and OATP1B1 polymorphisms
The ability of predicting severe adverse reactions caused by regorafenib is important. We evaluated regorafenib concentrations for adverse reaction risks and assessed the relevance of laboratory values and gene polymorphisms.
A total of 28 Japanese cancer patients who were treated with regorafenib were evaluated for the steady state of serum regorafenib concentrations and adverse reactions for 28 days. In addition, we determined the association of regorafenib concentrations with ABCG2 and OATP1B1 polymorphisms, which are regorafenib transporters.
Regorafenib concentrations were significantly higher in the group with Grade 2 or higher total bilirubin elevation and thrombocytopenia compared with the group with grades 0 or 1 [3.45 (2.18–7.31) vs. 1.76 (0.26–2.77) µg/mL, P = 0.01 and 3.45 (2.12–7.31) vs. 1.76 (0.26–2.77) µg/mL, P = 0.02, respectively]. A strong association was noted between serum regorafenib concentrations and total bilirubin levels, but the physical and genetic factors predicting regorafenib pharmacokinetics could not be clarified.
Regorafenib concentrations were associated with total bilirubin elevation and thrombocytopenia. Total serum bilirubin could be a useful marker when estimating regorafenib pharmacokinetics.
KeywordsAdverse reactions Bilirubin Pharmacokinetics Regorafenib OATP1B1 SLCO1B1
Compliance with ethical standards
Conflict of interest
The authors have no conflicts of interest to declare.
- 14.Zhao B, Zhao H (2017) Incidence and risk of regorafenib-induced hepatotoxicity. Oncotarget 8:84102–84111Google Scholar
- 18.Nozawa T, Minami H, Sugiura S et al (2005) Role of organic anion transporter OATP1B1 (OATP-C) in hepatic uptake of irinotecan and its active metabolite, 7-ethyl-10-hydroxycamptothecin: in vitro evidence and effect of single nucleotide polymorphisms. Drug Metab Dispos 33:434–439CrossRefGoogle Scholar
- 21.Ieiri I, Higuchi S, Sugiyama Y (2009) Genetic polymorphisms of uptake (OATP1B1, 1B3) and efflux (MRP2, BCRP) transporters: implications for inter-individual differences in the pharmacokinetics and pharmacodynamics of statins and other clinically relevant drugs. Expert Opin Drug Metab Toxicol 5:703–729CrossRefGoogle Scholar