Reduced indinavir exposure during pregnancy
Tim R Cressey, Brookie M Best, Jullapong Achalapong, Alice Stek, Jiajia Wang, Nantasak Chotivanich, Prapap Yuthavisuthi, Pornnapa Suriyachai, Sinart Prommas, David E Shapiro, D Heather Watts, Elizabeth Smith, Edmund Capparelli, Regis Kreitchmann, Mark Mirochnick, IMPAACT P1026s team, Elizabeth Hawkins, D Heather Watts, Sandra K Burchett, Francesca Aweeka, Steve Rossi, Michael Basar, Kathleen Kaiser, Emily Barr, Kenneth D Braun Jr, Jennifer Bryant, Kathleen A Medvik, Amy Jennings, Patcharee Kantipong, Jullapong Achalapong, Kannikar Saisawat, Chulapong Chanta, Kanchana Preedisripipat, Supaporn Utsaha, Chaniporn Yodsuwan, Pollawat Thongsuk, Yupawan Thaweesombat, Chureeratana Bowonwatanuwong, Nantasak Chotivanich, Suchat Hongsiriwon, Ladda Argadamnuy, Donyapattra Ekkomonrat, Prakit Yothipitak, Duangporn Wiwattanasorn, Somrat Matchua, Suluck Soontaros, Kessarin Chaisiri, Sinart Prommas, Prapaisri Layangool, Jutarat Mekmallika, Sommai Tratong, Ladda Ruluk, Titima Taweewattanapan, Marina Thitathan, Prapap Yuthavisuthi, Chaiwat Ngampiyaskul, Ubon Chanasit, Wanna Chamjamrat, Pathanee Teirsonsern, Nuttupassasorn Tungtongcha, Pisut Greetanukroh, Guttiga Halue, Wirawan Rasri, Pornnapa Suriyachai, Pornchai Techakunakorn, Kunlaya Jansook, Chutima Ruklao, Khanungnit Thungkham, Borwornluck Changlor, Wanpen Mooninta, Marc Lallemant, Gonzague Jourdain, Nicole Ngo-Giang-Huong, Pra-ornsuda Sukrakanchana, Kanchana Than-in-at, Nusara Krapunpongsakul, Renoo Wongsrisai, Patcharaporn Krueduangkam, Janjira Thonglo, Ruethai Wongchai, Tiwacha Thimakam, Purivis Chart, Yardpiroon Taworn, Pimpinun Punyati, Worathip Sripaoraya, Suriyan Tanasri, Tim R Cressey, Brookie M Best, Jullapong Achalapong, Alice Stek, Jiajia Wang, Nantasak Chotivanich, Prapap Yuthavisuthi, Pornnapa Suriyachai, Sinart Prommas, David E Shapiro, D Heather Watts, Elizabeth Smith, Edmund Capparelli, Regis Kreitchmann, Mark Mirochnick, IMPAACT P1026s team, Elizabeth Hawkins, D Heather Watts, Sandra K Burchett, Francesca Aweeka, Steve Rossi, Michael Basar, Kathleen Kaiser, Emily Barr, Kenneth D Braun Jr, Jennifer Bryant, Kathleen A Medvik, Amy Jennings, Patcharee Kantipong, Jullapong Achalapong, Kannikar Saisawat, Chulapong Chanta, Kanchana Preedisripipat, Supaporn Utsaha, Chaniporn Yodsuwan, Pollawat Thongsuk, Yupawan Thaweesombat, Chureeratana Bowonwatanuwong, Nantasak Chotivanich, Suchat Hongsiriwon, Ladda Argadamnuy, Donyapattra Ekkomonrat, Prakit Yothipitak, Duangporn Wiwattanasorn, Somrat Matchua, Suluck Soontaros, Kessarin Chaisiri, Sinart Prommas, Prapaisri Layangool, Jutarat Mekmallika, Sommai Tratong, Ladda Ruluk, Titima Taweewattanapan, Marina Thitathan, Prapap Yuthavisuthi, Chaiwat Ngampiyaskul, Ubon Chanasit, Wanna Chamjamrat, Pathanee Teirsonsern, Nuttupassasorn Tungtongcha, Pisut Greetanukroh, Guttiga Halue, Wirawan Rasri, Pornnapa Suriyachai, Pornchai Techakunakorn, Kunlaya Jansook, Chutima Ruklao, Khanungnit Thungkham, Borwornluck Changlor, Wanpen Mooninta, Marc Lallemant, Gonzague Jourdain, Nicole Ngo-Giang-Huong, Pra-ornsuda Sukrakanchana, Kanchana Than-in-at, Nusara Krapunpongsakul, Renoo Wongsrisai, Patcharaporn Krueduangkam, Janjira Thonglo, Ruethai Wongchai, Tiwacha Thimakam, Purivis Chart, Yardpiroon Taworn, Pimpinun Punyati, Worathip Sripaoraya, Suriyan Tanasri
Abstract
Aim: To describe the pharmacokinetics and safety of indinavir boosted with ritonavir (IDV/r) during the second and third trimesters of pregnancy and in the post-partum period.
Methods: IMPAACT P1026s is an on-going, prospective, non-blinded study of antiretroviral pharmacokinetics (PK) in HIV-infected pregnant women with a Thai cohort receiving IDV/r 400/100 mg twice daily during pregnancy through to 6-12 weeks post-partum as part of clinical care. Steady-state PK profiles were performed during the second (optional) and third trimesters and at 6-12 weeks post-partum. PK targets were the estimated 10(th) percentile IDV AUC (12.9 μg ml(-1)h) in non-pregnant historical Thai adults and a trough concentration of 0.1 μg ml(-1), the suggested minimum target.
Results: Twenty-six pregnant women were enrolled; thirteen entered during the second trimester. Median (range) age was 29.8 (18.9-40.8) years and weight 60.5 (50.0-85.0) kg at the third trimester PK visit. The 90% confidence limits for the geometric mean ratio of the indinavir AUC(0,12 h) and Cmax during the second trimester and post-partum (ante : post ratios) were 0.58 (0.49, 0.68) and 0.73 (0.59, 0.91), respectively; third trimester/post-partum AUC(0,12 h) and Cmax ratios were 0.60 (0.53, 0.68) and 0.63 (0.55, 0.72), respectively. IDV/r was well tolerated and 21/26 women had a HIV-1 viral load < 40 copies ml(-1) at delivery. All 26 infants were confirmed HIV negative.
Conclusion: Indinavir exposure during the second and third trimesters was significantly reduced compared with post-partum and ∼30% of women failed to achieve a target trough concentration. Increasing the dose of IDV/r during pregnancy to 600/100 mg twice daily may be preferable to ensure adequate drug concentrations.
Keywords: HIV; antiretrovirals; pregnancy; prevention of mother-to-child transmission.
© 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.
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Source: PubMed