Placental transfer and pharmacokinetics of lopinavir and other protease inhibitors in combination with nevirapine at delivery.
BACKGROUND
Antiretroviral combination therapies, including nevirapine (NVP) and protease inhibitors (PI), are increasingly used in the treatment and for the prophylaxis of vertical HIV-1 transmission in HIV-1 infected pregnant women.


OBJECTIVE
To determine pharmacokinetics and placental transfer of NVP and different PI in pregnancy we measured drug levels in maternal and foetal compartments at the day of delivery.


METHODS
We conducted a prospective study in 40 eligible HIV-1 infected pregnant women who gave birth in our hospital. A pre-dose to 6 h post-dose steady-state pharmacokinetic analysis (n = 35) of the drugs on the day of the scheduled Caesarean section was performed. In addition cord blood and amniotic fluid drug levels were measured (n = 40).


RESULTS
In all women NVP plasma concentrations (n = 20) were below the recommended level. PI plasma concentrations (nelfinavir, n = 5; saquinavir, n = 3; lopinavir, n = 10; ritonavir, n = 13) were extremely variable. Cord blood and amniotic fluid drug levels suggested that NVP passes the placenta unrestricted whereas PI were detected in smaller concentrations in the foetal compartment.


CONCLUSIONS
Because of the changed pharmacokinetics of antiretroviral drugs in pregnancy therapeutic drug monitoring could be important and dose adjustment should be considered. The minimal placental transfer of PI is desirable from the perspective that the foetus is protected from potentially teratogenic agents. However, it is not known if antiretroviral compounds in the foetal compartment contribute to the risk reduction of vertical HIV-1 transmission, and whether the property of missing placental transfer is in fact beneficial for the newborn.
Gingelmaier
Andrea
A
1st Department of Obstetrics and Gynecology, Ludwig-Maximilians-University of Munich, Maistrasse 11, 80337 Munich, Germany. andrea.gingelmaier@med.uni-muenchen.de
Kurowski
Michael
M
Kästner
Ralph
R
Eberle
Josef
J
Mylonas
Ioannis
I
Belohradsky
Bernd H
BH
Friese
Klaus
K
Grubert
Thomas A
TA
D000653:Amniotic Fluid / Q000737:chemistry; D023241:Antiretroviral Therapy, Highly Active; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D015658:HIV Infections / Q000517:prevention & control*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015497:HIV-1; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D061466:Lopinavir; D019829:Nevirapine / Q000008:administration & dosage; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000517:prevention & control*; D011446:Prospective Studies; D011744:Pyrimidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019562:Viral Load
D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019829:Nevirapine