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Placental transfer and pharmacokinetics of lopinavir and other protease inhibitors in combination with nevirapine at delivery

Gingelmaier, Andreaa; Kurowski, Michaelb; Kästner, Ralpha; Eberle, Josefc; Mylonas, Ioannisa; Belohradsky, Bernd Hd; Friese, Klausa; Grubert, Thomas Ae

doi: 10.1097/01.aids.0000242820.67001.2c
Clinical Science

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.

Design and 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.

From the a1st Department of Obstetrics and Gynecology, Ludwig-Maximilians-University of Munich, Germany

bAuguste-Viktoria-Krankenhaus, Berlin, Germany

cDepartment of Virology, Max-von-Pettenkofer-Institut, Ludwig-Maximilians-University of Munich, Germany

dDepartment of Pediatrics, Ludwig-Maximilians-University of Munich, Germany

eMedical Practice, Ravensburg.

Received 26 February, 2006

Accepted 12 June, 2006

Correspondence to A.Gingelmaier, 1st Department of Obstetrics and Gynecology, Ludwig-Maximilians-University, Maistrasse 11, 80337 Munich, Germany. Tel: +49 89 5160 4111; fax: +49 89 5160 4580; e-mail:

© 2006 Lippincott Williams & Wilkins, Inc.