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Reduced indinavir exposure during pregnancy
Author(s) -
Cressey Tim R.,
Best Brookie M.,
Achalapong Jullapong,
Stek Alice,
Wang Jiajia,
Chotivanich Nantasak,
Yuthavisuthi Prapap,
Suriyachai Pornnapa,
Prommas Sinart,
Shapiro David E.,
Watts D. Heather,
Smith Elizabeth,
Capparelli Edmund,
Kreitchmann Regis,
Mirochnick Mark
Publication year - 2013
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12078
Subject(s) - indinavir , medicine , cmax , pregnancy , pharmacokinetics , ritonavir , cmin , confidence interval , viral load , prospective cohort study , obstetrics , human immunodeficiency virus (hiv) , antiretroviral therapy , immunology , biology , genetics
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 C max 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 C max 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.