Maternal-fetal transfer and amniotic fluid accumulation of protease inhibitors in pregnant women who are infected with human immunodeficiency virus.
OBJECTIVE
The purpose of this study was to investigate placental transfer and amniotic fluid concentrations of protease inhibitors when they are given to pregnant women who are infected with human immunodeficiency virus.


METHODS
Fifty-eight mothers who received antiretroviral therapy that included > or =1 protease inhibitors for clinical indications at the time of delivery were enrolled in the study. Maternal blood samples and amniotic fluid were obtained during delivery or cesarean delivery, and paired cord blood samples were obtained by venipuncture immediately after the delivery. Drug concentrations were measured with high performance liquid chromatography.


RESULTS
Most maternal protease inhibitor plasma concentrations (38/66 concentrations) were below the trough concentrations that are recommended for therapeutic drug monitoring. Cord blood concentrations were below the assay limit of detection in 10 of 40 samples for nelfinavir and 25 of 40 samples for its metabolite M8, 9 of 11 samples for ritonavir, 4 of 6 samples for indinavir, 5 of 6 samples for saquinavir but were detectable in 3 of 3 samples for amprenavir. Among the 24 amniotic fluid samples that were available, the concentrations below the detection limit were 10 of 16 samples for nelfinavir, 11 of 16 samples for M8, 1 of 3 samples for indinavir, 4 of 4 samples for ritonavir, and 0 of 1 samples for amprenavir. There were significant correlations between cord blood and maternal concentrations of nelfinavir and its metabolite M8.


CONCLUSIONS
Placental transfer of the human immunodeficiency virus protease inhibitors is generally low; however, it may differ greatly according to the molecule.
Chappuy
Hélène
H
Pharmacologie Clinique, Université René-Descartes, Hôpital Cochin Saint-Vincent-de-Paul, 82 avenue Denfert Rochereau, 75674 Paris Cedex 14, France.
Tréluyer
Jean-Marc
JM
Rey
Elisabeth
E
Dimet
Jérôme
J
Fouché
Maria
M
Firtion
Ghislaine
G
Pons
Gérard
G
Mandelbrot
Laurent
L
D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism*; D002219:Carbamates; D004359:Drug Therapy, Combination; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000097:blood / Q000378:metabolism*; D006801:Humans; D019469:Indinavir / Q000097:blood / Q000378:metabolism; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D019888:Nelfinavir / Q000097:blood / Q000378:metabolism; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000378:metabolism*; D019438:Ritonavir / Q000097:blood / Q000378:metabolism; D019258:Saquinavir / Q000097:blood / Q000378:metabolism; D013449:Sulfonamides / Q000097:blood / Q000378:metabolism
D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C095108:amprenavir; D019469:Indinavir; D019888:Nelfinavir; D019258:Saquinavir; D019438:Ritonavir