Document Detail


Reduced indinavir exposure during pregnancy.
MedLine Citation:
PMID:  23305215     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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;
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  76     ISSN:  1365-2125     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-09-16     Completed Date:  2014-05-02     Revised Date:  2014-09-02    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  475-83     Citation Subset:  IM    
Copyright Information:
© 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Antiretroviral Therapy, Highly Active
Dose-Response Relationship, Drug
Female
HIV Infections / drug therapy,  metabolism*,  transmission
HIV Protease Inhibitors / administration & dosage,  blood,  pharmacokinetics*,  therapeutic use
Humans
Indinavir / administration & dosage,  blood,  pharmacokinetics*,  therapeutic use
Infant
Infant, Newborn
Infectious Disease Transmission, Vertical / prevention & control
Postpartum Period
Pregnancy
Pregnancy Complications, Infectious / drug therapy,  metabolism*,  virology
Pregnancy Trimester, Second
Pregnancy Trimester, Third
Prospective Studies
Ritonavir / administration & dosage,  blood,  pharmacokinetics*,  therapeutic use
Young Adult
Grant Support
ID/Acronym/Agency:
1 U01 AI068616/AI/NIAID NIH HHS; 5U01 AI41110/AI/NIAID NIH HHS; N01-DK-9-001/HHSN267200800001C/DK/NIDDK NIH HHS; U01 AI068616/AI/NIAID NIH HHS; U01 AI068632/AI/NIAID NIH HHS; U01AI068632/AI/NIAID NIH HHS; UM1 AI068616/AI/NIAID NIH HHS; UM1 AI068632/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/HIV Protease Inhibitors; 5W6YA9PKKH/Indinavir; O3J8G9O825/Ritonavir
Investigator
Investigator/Affiliation:
Elizabeth Hawkins / ; D Heather Watts / ; Sandra K Burchett / ; Francesca Aweeka / ; Steve Rossi / ; Michael Basar / ; Kathleen Kaiser / ; Emily Barr / ; Kenneth D Braun / ; 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 /
Comments/Corrections

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