Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Apr 1;83(4):373-380.
doi: 10.1097/QAI.0000000000002261.

Darunavir Pharmacokinetics With an Increased Dose During Pregnancy

Ahizechukwu C Eke  1 , Alice M Stek  2 , Jiajia Wang  3 , Regis Kreitchmann  4 , David E Shapiro  3 , Elizabeth Smith  5 , Nahida Chakhtoura  6 , Edmund V Capparelli  7 , Mark Mirochnick  8 , Brookie M Best  7 ; IMPAACT P1026s Protocol Team
Affiliations

Darunavir Pharmacokinetics With an Increased Dose During Pregnancy

Ahizechukwu C Eke et al. J Acquir Immune Defic Syndr. .

Abstract

Background: This study aims to evaluate the pharmacokinetics of an increased dose of darunavir (800 mg twice daily) with 100 mg ritonavir during pregnancy and postpartum.

Methods: Darunavir (DRV) and ritonavir (RTV; r) intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy (DRV/r 800/100 mg bid) and 2-3 weeks postpartum (DRV/r 600/100 mg twice daily). Plasma concentrations of darunavir and ritonavir were measured using high-performance liquid chromatography. Target darunavir area under the concentration time curve (AUC) was >70% (43.6 μg × h/mL) of median AUC (62.3 μg × h/mL) in nonpregnant adults on twice daily darunavir-ritonavir 600/100 mg.

Results: Twenty-four women were included in the analysis. Darunavir AUC0-12 was lower with the increased dose during the second {[geometric mean ratio (GMR) of 0.62 (IQR 0.44-0.88); P = 0.055]} and third trimesters [GMR 0.64 (IQR 0.55-0.73); P = <0.001] compared with postpartum. Darunavir apparent clearance was higher during the second [GMR 1.77 (IQR 1.24-2.51); P = 0.039] and third trimesters [GMR 2.01 (IQR 1.17-2.35); P = <0.001] compared with postpartum. Similarly, ritonavir AUC0-12 was lower during the third trimester [GMR 0.65 (IQR 0.52-0.82); P = 0.007] compared with postpartum, whereas its apparent clearance was higher during the third trimester [GMR 1.53 (IQR 1.22-1.92); P = 0.008] compared with postpartum. No major drug-related safety concerns were noted.

Conclusions: Increasing darunavir dose to 800 mg BID failed to significantly increase darunavir exposure compared with 600 mg BID. Other strategies, such as increasing the ritonavir dose should be investigated.

PubMed Disclaimer

Figures

Figure 1A:
Figure 1A:
Median darunavir concentrations. The 50th percentile data in this figure represents DRV/RTV 600 mg/100 mg BID in non-pregnant adults.
Figure 1B –
Figure 1B –
Darunavir area under the curve (AUC0–12)
Figure 1C:
Figure 1C:
Darunavir Apparent Clearance (CL/F).
Figure 1D:
Figure 1D:
Darunavir Cmax.
Figure 2:
Figure 2:
Median Ritonavir Concentrations.
See this image and copyright information in PMC

References

    1. Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs in Transmission in the United States. 2018; Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf Accessed Accessed 1/11/19.
    1. Feghali M, Venkataramanan R, Caritis S. Pharmacokinetics of drugs in pregnancy. Seminars in perinatology. 2015;39(7):512–519. - PMC - PubMed
    1. Eke AC, Dooley KE, Sheffield J. Pharmacologic Research in Pregnant Women – Time to Get it Right. The New England journal of medicine. 2019;380(14):1293–1295. - PMC - PubMed
    1. Crauwels HM, Kakuda TN, Ryan B, et al. Pharmacokinetics of once-daily darunavir/ritonavir in HIV-1-infected pregnant women. HIV Med. 2016;17(9):643–652. - PubMed
    1. Colbers A, Molto J, Ivanovic J, et al. Pharmacokinetics of total and unbound darunavir in HIV-1-infected pregnant women. J Antimicrob Chemother. 2015;70(2):534–542. - PubMed

Publication types

MeSH terms