Significant pharmacokinetic interactions between artemether/lumefantrine and efavirenz or nevirapine in HIV-infected Ugandan adults.
Significant pharmacokinetic interactions between artemether/lumefantrine and efavirenz or nevirapine in HIV-infected Ugandan adults.
复制标题
DOI：
10.1093/jac/dks207
复制
发表时间：
2012-09
期刊：
影响因子：
--
通讯作者：
Merry C
中科院分区：
文献类型：
--
作者：
Byakika-Kibwika P;Lamorde M;Mayito J;Nabukeera L;Namakula R;Mayanja-Kizza H;Katabira E;Ntale M;Pakker N;Ryan M;Hanpithakpong W;Tarning J;Lindegardh N;de Vries PJ;Khoo S;Back D;Merry C
蒿甲醚/苯芴醇与抗逆转录病毒治疗联合给药可能发生药代动力学药物相互作用。我们研究了蒿甲醚/苯芴醇与依法韦仑或奈韦拉平之间的药物相互作用。我们进行了一项交叉研究，其中HIV感染的成人在依非韦伦或奈韦拉平稳态之前和稳态时接受标准的6剂蒿甲醚/本芴醇80/480 mg。测定并比较蒿甲醚、双氢青蒿素、苯芴醇、依法韦仑和奈韦拉平的血浆浓度。依法韦仑显著降低了蒿甲醚的最大浓度（Cmax）和血浆AUC（中位数29 vs 12 ng/mL，P <0.01，119 vs 25 ng·h/mL，P <0.01）、双氢青蒿素Cmax和AUC（中位数120 vs 26 ng/mL，P <0.01，341 vs 84 ng·h/mL，P <0.01）以及本芴醇Cmax和AUC（中位数8737 vs 6331 ng/mL，P = 0.03，280 370 vs 124 381 ng·h/mL，P <0.01）。 奈韦拉平显著降低了蒿甲醚的Cmax和AUC（中位数28 vs 11 ng/mL，P <0.01，123 vs 34 ng·h/mL，P <0.01）和双氢青蒿素的Cmax和AUC（中位数107 vs 59 ng/mL，P <0.01，364 vs 228 ng·h/mL，P <0.01）。 奈韦拉平未显著降低本芴醇的Cmax和AUC。蒿甲醚/苯芴醇降低奈韦拉平的Cmax和AUC（中位数8620 vs 4958 ng/mL，P <0.01;中位数66329 vs 35728 ng·h/mL，P <0.01），但不影响依法韦仑的暴露量。 蒿甲醚/本芴醇与依非韦伦或奈韦拉平联合给药导致蒿甲醚、双氢青蒿素、本芴醇和奈韦拉平暴露减少。这些药物相互作用可能会增加疟疾治疗失败的风险，并增加对蒿甲醚/苯芴醇和奈韦拉平产生耐药性的风险。迫切需要从群体药代动力学和药效学试验中获得临床数据，以评估这些药物相互作用的影响。
Co-administration of artemether/lumefantrine with antiretroviral therapy has potential for pharmacokinetic drug interactions. We investigated drug–drug interactions between artemether/lumefantrine and efavirenz or nevirapine. We performed a cross-over study in which HIV-infected adults received standard six-dose artemether/lumefantrine 80/480 mg before and at efavirenz or nevirapine steady state. Artemether, dihydroartemisinin, lumefantrine, efavirenz and nevirapine plasma concentrations were measured and compared. Efavirenz significantly reduced artemether maximum concentration (Cmax) and plasma AUC (median 29 versus 12 ng/mL, P < 0.01, and 119 versus 25 ng · h/mL, P < 0.01), dihydroartemisinin Cmax and AUC (median 120 versus 26 ng/mL, P < 0.01, and 341 versus 84 ng · h/mL, P < 0.01), and lumefantrine Cmax and AUC (median 8737 versus 6331 ng/mL, P = 0.03, and 280 370 versus 124 381 ng · h/mL, P < 0.01). Nevirapine significantly reduced artemether Cmax and AUC (median 28 versus 11 ng/mL, P < 0.01, and 123 versus 34 ng · h/mL, P < 0.01) and dihydroartemisinin Cmax and AUC (median 107 versus 59 ng/mL, P < 0.01, and 364 versus 228 ng · h/mL, P < 0.01). Lumefantrine Cmax and AUC were non-significantly reduced by nevirapine. Artemether/lumefantrine reduced nevirapine Cmax and AUC (median 8620 versus 4958 ng/mL, P < 0.01, and 66 329 versus 35 728 ng · h/mL, P < 0.01), but did not affect efavirenz exposure. Co-administration of artemether/lumefantrine with efavirenz or nevirapine resulted in a reduction in artemether, dihydroartemisinin, lumefantrine and nevirapine exposure. These drug interactions may increase the risk of malaria treatment failure and development of resistance to artemether/lumefantrine and nevirapine. Clinical data from population pharmacokinetic and pharmacodynamic trials evaluating the impact of these drug interactions are urgently needed.
登录
查看更多内容
DOI：
10.1111/j.1365-2125.1994.tb04271.x
发表时间：
1994-03-01
影响因子：
3.4
作者：
BANGCHANG, KN;KARBWANG, J;EDWARDS, G
通讯作者：
EDWARDS, G
影响因子：
3.8
作者：
French, N;Nakiyingi, J;Gilks, CF
通讯作者：
Gilks, CF
影响因子：
4.9
作者：
Kredo, T.;Mauff, K.;Barnes, K. I.
通讯作者：
Barnes, K. I.
影响因子：
6.7
作者：
Almond, LM;Edirisinghe, D;Khoo, SH
通讯作者：
Khoo, SH
影响因子：
4.3
作者：
Ma, Qing;Okusanya, Olanrewaju O;Morse, Gene D
通讯作者：
Morse, Gene D