Inhibition of paracetamol glucuronidation by tyrosine kinase inhibitors

被引：53
作者：
Liu, Yong
Ramirez, Jacqueline
Ratain, Mark J. [1 ,2 ,3 ]
机构：
[1] Univ Chicago, Hematol Oncol Sect, Dept Med, Chicago, IL 60637 USA
[2] Univ Chicago, Dept Comm Clin Pharmacol & Pharmacogenom, Chicago, IL 60637 USA
[3] Univ Chicago, Comprehens Res Ctr, Chicago, IL 60637 USA
来源：
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY | 2011年 / 71卷 / 06期
基金：
美国国家卫生研究院;
关键词：
acetaminophen; inhibition; paracetamol; toxicity; tyrosine kinase inhibitors; UDP-glucuronosyltransferase; HUMAN LIVER-MICROSOMES; UDP-GLUCURONOSYLTRANSFERASES; ACETAMINOPHEN GLUCURONIDATION; HEPATOTOXICITY; FAILURE;
D O I：
10.1111/j.1365-2125.2011.03911.x
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
AIMS We aimed to investigate the effects of tyrosine kinase inhibitors (TKIs) on paracetamol (acetaminophen) glucuronidation. METHODS The inhibition of nine small molecule TKIs on paracetamol glucuronidation was investigated in human liver microsomes (HLMs) and recombinant human UDP-glucuronosyltransferases (UGTs). RESULTS Sorafenib, dasatinib and imatinib exhibited mixed inhibition against paracetamol glucuronidation in pooled HLMs, and potent inhibition in UGT1A9 and UGT2B15. Dasatinib and imatinib also inhibited UGT1A1-mediated paracetamol glucuronidation. Axitinib, erlotinib, gefitinib, lapatinib, nilotinib and vandetanib exhibited weak inhibition of paracetamol glucuronidation activity in HLMs. CONCLUSIONS The inhibition of paracetamol glucuronidation by TKIs might be of particular concern when they are co-administered.
引用
收藏
页码：917 / 920
页数：4
相关论文
共 14 条
[1]   High-performance liquid chromatographic assay for acetaminophen glucuronide in human liver microsomes [J].
Alkharfy, KM ;
Frye, RF .
JOURNAL OF CHROMATOGRAPHY B, 2001, 753 (02) :303-308
[2]   Role of tyrosine kinase inhibitors in cancer therapy [J].
Arora, A ;
Scholar, EM .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2005, 315 (03) :971-979
[3]  
Copeland RA, 2000, ENZYMES PRACTICAL IN
[4]  
Court MH, 2001, J PHARMACOL EXP THER, V299, P998
[5]   ENHANCED ACETAMINOPHEN TOXICITY IN RATS WITH BILIRUBIN GLUCURONYL TRANSFERASE DEFICIENCY [J].
DEMORAIS, SMF ;
WELLS, PG .
HEPATOLOGY, 1989, 10 (02) :163-167
[6]   Phenobarbital and phenytoin increased acetaminophen hepatotoxicity due to inhibition of UDP-glucuronosyltransferases in cultured human hepatocytes [J].
Kostrubsky, SE ;
Sinclair, JF ;
Strom, SC ;
Wood, S ;
Urda, E ;
Stolz, DB ;
Wen, YH ;
Kulkarni, S ;
Mutlib, A .
TOXICOLOGICAL SCIENCES, 2005, 87 (01) :146-155
[7]   Comparison of the Drug-Drug Interactions Potential of Erlotinib and Gefitinib via Inhibition of UDP-Glucuronosyltransferases [J].
Liu, Yong ;
Ramirez, Jacqueline ;
House, Larry ;
Ratain, Mark J. .
DRUG METABOLISM AND DISPOSITION, 2010, 38 (01) :32-39
[8]   DETERMINANTS OF ACETAMINOPHEN METABOLISM - EFFECT OF INDUCERS AND INHIBITORS OF DRUG-METABOLISM ON ACETAMINOPHENS METABOLIC PATHWAYS [J].
MINERS, JO ;
ATTWOOD, J ;
BIRKETT, DJ .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1984, 35 (04) :480-486
[9]   Results from an in vitro and a clinical/pharmacological phase I study with the combination irinotecan and sorafenib [J].
Mross, K. ;
Steinbild, S. ;
Baas, F. ;
Gmehling, D. ;
Radtke, M. ;
Voliotis, D. ;
Brendel, E. ;
Christensen, O. ;
Unger, C. .
EUROPEAN JOURNAL OF CANCER, 2007, 43 (01) :55-63
[10]   Kinetics of acetaminophen glucuronidation by UDP-glucuronosyltransferases 1A1, 1A6, 1A9 and 2B15. Potential implications in acetaminophen-induced hepatotoxicity [J].
Mutlib, AE ;
Goosen, TC ;
Bauman, JN ;
Williams, JA ;
Kulkarni, S ;
Kostrubsky, S .
CHEMICAL RESEARCH IN TOXICOLOGY, 2006, 19 (05) :701-709
12