Pharmacokinetics and Drug-Drug Interactions of Isoniazid and Efavirenz in Pregnant Women Living With HIV in High TB Incidence Settings: Importance of Genotyping

被引：26

作者：

Gausi, Kamunkhwala ^{[1
]}

Wiesner, Lubbe ^{[1
]}

Norman, Jennifer ^{[1
]}

Wallis, Carole L. ^{[2
]}

Onyango-Makumbi, Carolyne ^{[3
]}

Chipato, Tsungai ^{[4
]}

Haas, David W. ^{[5
,6
,7
,8
,9
,10
]}

Browning, Renee ^{[11
]}

Chakhtoura, Nahida ^{[12
]}

Montepiedra, Grace ^{[13
]}

Aaron, Lisa ^{[13
]}

McCarthy, Katie ^{[14
]}

Bradford, Sarah ^{[14
]}

Vhembo, Tichaona ^{[4
]}

Stranix-Chibanda, Lynda ^{[4
]}

Masheto, Gaerolwe R. ^{[15
]}

Violari, Avy ^{[16
]}

Mmbaga, Blandina T. ^{[17
]}

Aurpibul, Linda ^{[18
]}

Bhosale, Ramesh ^{[19
]}

Nevrekhar, Neetal ^{[20
]}

Rouzier, Vanessa ^{[21
,22
]}

Kabugho, Enid ^{[23
]}

Mutambanengwe, Mercy ^{[24
]}

Chanaiwa, Vongai ^{[24
]}

Nyati, Mandisa ^{[16
]}

Mhembere, Tsungai ^{[24
]}

Tongprasert, Fuanglada ^{[25
]}

Hesseling, Anneke ^{[26
]}

Shin, Katherine ^{[11
]}

Zimmer, Bonnie ^{[27
]}

Costello, Diane ^{[28
]}

Jean-Philippe, Patrick ^{[11
]}

Sterling, Timothy R. ^{[29
]}

Theron, Gerhard ^{[30
]}

Weinberg, Adriana ^{[31
]}

Gupta, Amita ^{[32
]}

Denti, Paolo ^{[1
]}

机构：

[1] Univ Cape Town, Div Clin Pharmacol, Dept Med, Cape Town, South Africa

[2] BARC Labs South Africa, Johannesburg, South Africa

[3] Johns Hopkins Univ Res Collaborat, Makerere Univ, Kampala, Uganda

[4] Univ Zimbabwe, Dept Obstet & Gynaecol, Coll Hlth Sci, Harare, Zimbabwe

[5] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA

[6] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA

[7] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37212 USA

[8] Vanderbilt Univ, Sch Med, Dept Microbiol, Nashville, TN 37212 USA

[9] Vanderbilt Univ, Sch Med, Dept Immunol, Nashville, TN 37212 USA

[10] Meharry Med Coll, Dept Internal Med, Nashville, TN 37208 USA

[11] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA

[12] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA

[13] Harvard TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA USA

[14] FHI 360, Durham, NC USA

[15] Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana

[16] Univ Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South Africa

[17] Kilimanjaro Christian Med Ctr, Moshi, Tanzania

[18] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai, Thailand

[19] Byramjee Jeejeebhoy Govt Med Coll, Pune, Maharashtra, India

[20] Johns Hopkins Clin Res Site, Byramjee Jeejeebhoy Govt College, Pune, Maharashtra, India

[21] Weill Cornell Ctr, Global Hlth New York, New York, NY USA

[22] Ctr GHESKIO, Port Au Prince, Haiti

[23] MU JHU Res Collaborat, Kampala, Uganda

[24] Univ Zimbabwe, Coll Hlth Sci, Clin Trials Res Ctr, Harare, Zimbabwe

[25] Chiang Mai Univ, Dept Obstet & Gynecol, Fac Med, Chiang Mai, Thailand

[26] Stellenbosch Univ, Desmond Tutu TB Ctr, Dept Paediat & Child Hlth, Tygerberg, South Africa

[27] Univ Calif Los Angeles, Los Angeles, CA USA

[28] Frontier Sci Fdn, Amherst, NY USA

[29] Vanderbilt Univ, Med Ctr, Vanderbilt TB Ctr, Nashville, TN USA

[30] Stellenbosch Univ, Dept Obstet & Gynaecol, Cape Town, South Africa

[31] Univ Colorado Denver, Anschutz Med Campus, Aurora, CO USA

[32] Johns Hopkins Univ, Sch Med, Baltimore, MD USA

[33] Res Grp IMPAACT P1078, Study Grp Team, Durham, NC USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2021年 / 109卷 / 04期

基金：

美国国家卫生研究院;

关键词：

NAT2; GENOTYPE; CYP2B6; MODEL; PHARMACOGENETICS; IMPLEMENTATION; TUBERCULOSIS; METABOLISM; PHENOTYPE; THERAPY;

D O I：

10.1002/cpt.2044

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The World Health Organization guidelines recommend that individuals living with HIV receive >= 6 months of isoniazid preventive therapy, including pregnant women. Yet, plasma isoniazid exposure during pregnancy, in the antiretroviral therapy era, has not been well-described. We investigated pregnancy-induced and pharmacogenetic-associated pharmacokinetic changes and drug-drug interactions between isoniazid and efavirenz in pregnant women. Eight hundred forty-seven women received isoniazid for 28 weeks, either during pregnancy or at 12 weeks postpartum, and 786 women received efavirenz. After adjusting forNAT2andCYP2B6genotype and weight, pregnancy increased isoniazid and efavirenz clearance by 26% and 15%, respectively. Isoniazid decreased efavirenz clearance by 7% inCYP2B6normal metabolizers and 13% in slow and intermediate metabolizers. Overall, both isoniazid and efavirenz exposures were reduced during pregnancy, but the main determinants of drug concentration wereNAT2andCYP2B6genotypes, which resulted in a five-fold difference for both drugs between rapid and slow metabolizers.

引用

页码：1034 / 1044

页数：11

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