伊马替尼药动学相关的药物相互作用研究进展
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摘要
伊马替尼是治疗慢性粒细胞白血病的一线药物,它在体内经多种CYP450代谢酶和转运体作用,临床多种合用药物可能通过不同的相互作用机制改变其在体内的过程,甚至引起显著的临床意义。本文综述并探讨了不同种类药物对伊马替尼药代动力学的影响,促进伊马替尼的临床安全、有效用药。
Imatinib, the first line treatment of chronic myelocytic leukemia, is affected by various CYP450 metabolic enzymes and transporters in pharmacokinetic process. Many clinical combination drugs may change its process in vivo by different drug-drug interaction, and even cause significant clinical significance. This article reviews and discusses the effects of different kinds of drugs on the pharmacokinetics of imatinib, so as to ensure the clinical safety and effectiveness of imatinib.
Imatinib, the first line treatment of chronic myelocytic leukemia, is affected by various CYP450 metabolic enzymes and transporters in pharmacokinetic process. Many clinical combination drugs may change its process in vivo by different drug-drug interaction, and even cause significant clinical significance. This article reviews and discusses the effects of different kinds of drugs on the pharmacokinetics of imatinib, so as to ensure the clinical safety and effectiveness of imatinib.
引文
[1]PENG B,LLOYD P,SCHRAN H.Clinical pharmacokinetics of imatinib[J].Clin Pharmacokinet,2005,44(9):879-894.
[2]NEBOT N,CRETTOL S,D’ESPOSITO F,et al.Participation of CYP2C8 and CYP3A4 in the N-demethylation of imatinib in human hepatic microsomes[J].Br J Pharmcol,2010,161(5):1059-1069.
[3]O’BRIEN S G,MEINHARDT P,NOND E,et al.Effect of imatinib mesylate(STI571,Glivec)on the pharmacokinetics of simvastatin,a cytochrome P450 3A4 substrate,in patients with chronic myeloid leukaemia[J].Br J Cancer,2003,89(10):1855-1859.
[4]ATIQ F,BROERS A E C,ANDREWS L M,et al.A clinically relevant pharmacokinetic interaction between cyclosporine and imatinib[J].Eur J Clin Pharmcol,2016,72(7):719-723.
[5]RENARD D,BOUILLON T,ZHOU G,et al.Pharmacokinetic interactions among imatinib,bosentan and sildenafil,and their clinical implications in severe pulmonary arterial hypertension[J].Br J Clin Pharmcol,2015,80(1):75-85.
[6]HAMADA A,MIYANO H,WATANABE H,et al.Interaction of imatinibmesilate with human P-glycoprotein[J].JPharmacol Exp Ther,2003,307(2):824-828.
[7]HU S,FRANKE R M,FILIPSKI K K,et al.Interaction of imatinib with human organic ion carriers[J].Clin Cancer Res,2008,14(10):3141-3148.
[8]SPARANO B A,EGORIN M J,PARISE R A,et al.Effect of antacid on imatinibabsorption[J].Cancer Chemother Pharmacol,2009,63(3):525-528.
[9]EGORIN M J,SHAH D D,CHRISTNER S M,et al.Effect of a proton pump inhibitor on the pharmacokinetics of imatinib[J].Br J ClinPharmacol,2009,68(3):370-374.
[10]BREEDVELD P,PLUIM D,CIPRIANI G,et al.The effect of Bcrp1(Abcg2)on the in vivo pharmacokinetics and brain penetration of imatinibmesylate(Gleevec):implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain enetration of imatinib in patients[J].Cancer Res,2005,65(7):2577-2582.
[11]OOSTENDORP R L,BUCKLE T,BEIJNEN J H,et al.The effect of P-gp(Mdr1a/1b),BCRP(Bcrp1)and P-gp/BCRPinhibitors on the in vivo absorption,distribution,metabolism and excretion of imatinib[J].Invest New Drug,2009,27(1):31-40.
[12]DARBALAEI S,ZHANG X,WANG N,et al.Effects of aprepitant on the pharmacokinetics of imatinib and its main metabolite in rats[J].Pharmazie,2018,73(6):329-334.
[13]BEUMER J H,PILLAI V C,PARISE R A,et al.Human hepatocyte assessment of imatinib drug-drug interantionscomplexities in clinical translation[J].Br J Clin Pharmacol,2015,80(5):1097-1108.
[14]BOLTON A E,PENG B,HUBERT M,et al.Effect of rifampicin on the pharmacokinetics of imatinib mesylate(Gleevec,STI571)in healthy subjects[J].Cancer Chemother Pharmacol,2004,53(2):102-106.
[15]DUTREIX C,PENG B,MEHRING G,et al.Pharmacokinetic interaction between ketoconazole and imatinib mesylate(Glivec)in healthy subjects[J].Cancer Chemother Pharmacol,2004,54(4):290-294.
[16]VAN ERP N P,GELDERBLOM H,KARLSSON M O,et al.Influence of CYP3A4 inhibition on the steady-state pharmacokinetics of imatinib[J].Clin Cancer Res,2007,13(24):7394-7400.
[17]FILPPULA A M,NEUVONEN M,LAITILA J,et al.Autoinhibition of CYP3A4 leads to important role of CYP2C8in imatinib metabolism:variability in CYP2C8 activity may alter plasma concentrations and respose[J].Drug Metab Dispos,2013,41(1):50-59.
[18]FILPPULA A M,TORNIO A,NIEMI M,et al.Gemfibrozil impairs imatinib absorption and inhibits the CYP2C8-mediated formation of its main metabolite[J].Clin Pharmacol Ther,2013,94(3):383-393.
[19]BARRATT D T,COX H K,MENELAOU A,et al.CYP2C8genotype significantly alters imatinib metabolism in chronic myeloid leukaemia patients[J].Clin Pharmacokinet,2017,56(8):977-985.
[20]GROLL A H,TOWNSEND R,DESAI A,et al.Drug-drug interactions between triazole antifungal agents used to treat invasive aspergillosis and immunosuppressants metabolized by cytochrome P450 3A4[J].Transpl Infect Dis,2017,19(5).doi:10.1111/tid.12751.Epub 2017 sep 28.
[21]LUO X,LI T,YU Z,et al.The impact of azole antifungal drugs on imatinib metabolism in human liver microsomes[J].Xenobiotica,2019,49(7):753-761.
[22]LIN G,WANG C,QIU X,et al.Differential effects of ketoconazole,itraconazole and voriconazole on the pharmacokinetics of imatinib and its main metabolite GCP74588 in rat[J].Drug Dev Ind Pharm,2014,40(12):1616-1622.
[23]TAN S Y,KAN E,LIM W Y,et al.Metronidazole leads to enhanced uptake of imatinib in brain,liver and kidney without affecting its plasma pharmacokinetics in mice[J].J Pharm Pharmacol,2011,63(7):918-925.
[24]WEN P Y,YUNG W K,LAMBORN K R,et al.PhaseⅠ/Ⅱstudy of imatinib mesylate for recurrent malignant gliomas:North American Brain Tumor Consortium Study 99-08[J].Clin Cancer Res,2006,12(16):4899-4907.
[25]PURSCHE S,SCHLEYER E,VON BONIN M,et al.Influence of enzyme-inducing antiepileptic drugs on trough level of imatinib in glioblastoma patients[J].Curr Clin Pharmacol,2008,3(3):198-203.
[26]FRYE R F,FITZGERALD S M,LAGATTUTA T F,et al.Effect of St John’s wort on imatinib mesylate pharmacokinetics[J].Clin Pharmacol Ther,2004,76(4):323-329.
[27]SMITH P F,BULLOCK J M,BOOKER B M,et al.The influence of St.John’s wort on the pharmacokinetics and protein binding of imatinib mesylat[J].Pharmacotherapy,2004,24(11):1508-1514.
[28]WANG L,WANG Z,XIA M M,et al.Inhibitory effect of silybin on pharmacokinetics of imatinib in vivo and in vitro[J].Can J Physiol Pharmacol,2014,92(11):961-964.
[29]LIU X Y,XU T,LI W S,et al.The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats[J].Biomed Res Int,2013:789184.Published online 2013 Nov 28.Doi:10.1155/2013/789184.
[30]WANG Z,WANG L,XIA M M,et al.Pharmacokinetics interaction between imatinib and genistein in rats[J].Biomed Res Int,2015:368976.Published online 2015 Jan 5.Doi:10.1155/2015/368976.
[31]KIMURA S,KAKO S,WADA H,et al.Can grapefruit juice decrease the cost of imatinib for the treatment of chronic myelogenous leukemia?[J].Leuk Res,2011,35(1):e11-e12.
[2]NEBOT N,CRETTOL S,D’ESPOSITO F,et al.Participation of CYP2C8 and CYP3A4 in the N-demethylation of imatinib in human hepatic microsomes[J].Br J Pharmcol,2010,161(5):1059-1069.
[3]O’BRIEN S G,MEINHARDT P,NOND E,et al.Effect of imatinib mesylate(STI571,Glivec)on the pharmacokinetics of simvastatin,a cytochrome P450 3A4 substrate,in patients with chronic myeloid leukaemia[J].Br J Cancer,2003,89(10):1855-1859.
[4]ATIQ F,BROERS A E C,ANDREWS L M,et al.A clinically relevant pharmacokinetic interaction between cyclosporine and imatinib[J].Eur J Clin Pharmcol,2016,72(7):719-723.
[5]RENARD D,BOUILLON T,ZHOU G,et al.Pharmacokinetic interactions among imatinib,bosentan and sildenafil,and their clinical implications in severe pulmonary arterial hypertension[J].Br J Clin Pharmcol,2015,80(1):75-85.
[6]HAMADA A,MIYANO H,WATANABE H,et al.Interaction of imatinibmesilate with human P-glycoprotein[J].JPharmacol Exp Ther,2003,307(2):824-828.
[7]HU S,FRANKE R M,FILIPSKI K K,et al.Interaction of imatinib with human organic ion carriers[J].Clin Cancer Res,2008,14(10):3141-3148.
[8]SPARANO B A,EGORIN M J,PARISE R A,et al.Effect of antacid on imatinibabsorption[J].Cancer Chemother Pharmacol,2009,63(3):525-528.
[9]EGORIN M J,SHAH D D,CHRISTNER S M,et al.Effect of a proton pump inhibitor on the pharmacokinetics of imatinib[J].Br J ClinPharmacol,2009,68(3):370-374.
[10]BREEDVELD P,PLUIM D,CIPRIANI G,et al.The effect of Bcrp1(Abcg2)on the in vivo pharmacokinetics and brain penetration of imatinibmesylate(Gleevec):implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain enetration of imatinib in patients[J].Cancer Res,2005,65(7):2577-2582.
[11]OOSTENDORP R L,BUCKLE T,BEIJNEN J H,et al.The effect of P-gp(Mdr1a/1b),BCRP(Bcrp1)and P-gp/BCRPinhibitors on the in vivo absorption,distribution,metabolism and excretion of imatinib[J].Invest New Drug,2009,27(1):31-40.
[12]DARBALAEI S,ZHANG X,WANG N,et al.Effects of aprepitant on the pharmacokinetics of imatinib and its main metabolite in rats[J].Pharmazie,2018,73(6):329-334.
[13]BEUMER J H,PILLAI V C,PARISE R A,et al.Human hepatocyte assessment of imatinib drug-drug interantionscomplexities in clinical translation[J].Br J Clin Pharmacol,2015,80(5):1097-1108.
[14]BOLTON A E,PENG B,HUBERT M,et al.Effect of rifampicin on the pharmacokinetics of imatinib mesylate(Gleevec,STI571)in healthy subjects[J].Cancer Chemother Pharmacol,2004,53(2):102-106.
[15]DUTREIX C,PENG B,MEHRING G,et al.Pharmacokinetic interaction between ketoconazole and imatinib mesylate(Glivec)in healthy subjects[J].Cancer Chemother Pharmacol,2004,54(4):290-294.
[16]VAN ERP N P,GELDERBLOM H,KARLSSON M O,et al.Influence of CYP3A4 inhibition on the steady-state pharmacokinetics of imatinib[J].Clin Cancer Res,2007,13(24):7394-7400.
[17]FILPPULA A M,NEUVONEN M,LAITILA J,et al.Autoinhibition of CYP3A4 leads to important role of CYP2C8in imatinib metabolism:variability in CYP2C8 activity may alter plasma concentrations and respose[J].Drug Metab Dispos,2013,41(1):50-59.
[18]FILPPULA A M,TORNIO A,NIEMI M,et al.Gemfibrozil impairs imatinib absorption and inhibits the CYP2C8-mediated formation of its main metabolite[J].Clin Pharmacol Ther,2013,94(3):383-393.
[19]BARRATT D T,COX H K,MENELAOU A,et al.CYP2C8genotype significantly alters imatinib metabolism in chronic myeloid leukaemia patients[J].Clin Pharmacokinet,2017,56(8):977-985.
[20]GROLL A H,TOWNSEND R,DESAI A,et al.Drug-drug interactions between triazole antifungal agents used to treat invasive aspergillosis and immunosuppressants metabolized by cytochrome P450 3A4[J].Transpl Infect Dis,2017,19(5).doi:10.1111/tid.12751.Epub 2017 sep 28.
[21]LUO X,LI T,YU Z,et al.The impact of azole antifungal drugs on imatinib metabolism in human liver microsomes[J].Xenobiotica,2019,49(7):753-761.
[22]LIN G,WANG C,QIU X,et al.Differential effects of ketoconazole,itraconazole and voriconazole on the pharmacokinetics of imatinib and its main metabolite GCP74588 in rat[J].Drug Dev Ind Pharm,2014,40(12):1616-1622.
[23]TAN S Y,KAN E,LIM W Y,et al.Metronidazole leads to enhanced uptake of imatinib in brain,liver and kidney without affecting its plasma pharmacokinetics in mice[J].J Pharm Pharmacol,2011,63(7):918-925.
[24]WEN P Y,YUNG W K,LAMBORN K R,et al.PhaseⅠ/Ⅱstudy of imatinib mesylate for recurrent malignant gliomas:North American Brain Tumor Consortium Study 99-08[J].Clin Cancer Res,2006,12(16):4899-4907.
[25]PURSCHE S,SCHLEYER E,VON BONIN M,et al.Influence of enzyme-inducing antiepileptic drugs on trough level of imatinib in glioblastoma patients[J].Curr Clin Pharmacol,2008,3(3):198-203.
[26]FRYE R F,FITZGERALD S M,LAGATTUTA T F,et al.Effect of St John’s wort on imatinib mesylate pharmacokinetics[J].Clin Pharmacol Ther,2004,76(4):323-329.
[27]SMITH P F,BULLOCK J M,BOOKER B M,et al.The influence of St.John’s wort on the pharmacokinetics and protein binding of imatinib mesylat[J].Pharmacotherapy,2004,24(11):1508-1514.
[28]WANG L,WANG Z,XIA M M,et al.Inhibitory effect of silybin on pharmacokinetics of imatinib in vivo and in vitro[J].Can J Physiol Pharmacol,2014,92(11):961-964.
[29]LIU X Y,XU T,LI W S,et al.The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats[J].Biomed Res Int,2013:789184.Published online 2013 Nov 28.Doi:10.1155/2013/789184.
[30]WANG Z,WANG L,XIA M M,et al.Pharmacokinetics interaction between imatinib and genistein in rats[J].Biomed Res Int,2015:368976.Published online 2015 Jan 5.Doi:10.1155/2015/368976.
[31]KIMURA S,KAKO S,WADA H,et al.Can grapefruit juice decrease the cost of imatinib for the treatment of chronic myelogenous leukemia?[J].Leuk Res,2011,35(1):e11-e12.