710 
Adequate Lopinavir Exposure Achieved with a Higher Dose during the Third Trimester of Pregnancy
Mark Mirochnick*1, A Stek2, E Capparelli3, B Best3, D Holland3, J Connor3, S Burchett4, C Hu5, E Smith6, J Read7, and PACTG 1026s Protocol Team
1Boston Univ Sch of Publ Hlth, MA, US; 2David Geffen Sch of Med, Univ of California, Los Angeles Med Ctr, US; 3Univ of California, San Diego, US; 4Children’s Hosp, Boston, MA, US; 5Harvard Sch of Publ Hlth, Boston, MA, US; 6NIAID, NIH, DHHS, Bethesda, MD, US; and 7Natl Inst Child Hlth and Devt, NIH, DHHS, Bethesda, MD, US
Background: Use of standard adult lopinavir/ritonavir
(LPV/r) dosing (400 mg/100 mg) during the third trimester of pregnancy results
in reduced LPV exposure. Optimal ART exposure during pregnancy is critical for
prevention of HIV mother to child transmission (MTCT) and for maternal health.
The goal of this analysis was to determine LPV exposure during the third
trimester of pregnancy and 2 weeks postpartum with a higher LPV/r dose.
Methods: PACTG 1026s is an ongoing, prospective,
non-blinded study of ART pharmacokinetics in HIV-infected pregnant women that
includes a cohort receiving LPV/r 400 mg/100 mg twice daily during the second
trimester, and 533 mg/133 mg twice daily during the third trimester through 2
weeks postpartum. Intensive steady-state 12-hour pharmacokinetic profiles were
performed during the third trimester and at 2 weeks postpartum, and were
optional during the second trimester. Maternal and umbilical cord blood samples
were obtained at delivery. LPV was measured by reverse-phase high-performance
liquid chromatography (HPLC) with a detection limit of 0.05 mg/mL. Target LPV AUC was > estimated 10th
percentile LPV AUC (>52mg*hr/mL) in non-pregnant
historical controls taking the standard dose (mean AUC=80mg*hr/mL).
Results: As of
September 2005, LPV pharmacokinetic data were available for 23 women (7
black, 10 Hispanic, 5 white, 1 other; median age 31.9 years, median delivery
weight, 79.1 kg). AUC and Cmin were
significantly lower in third trimester compared with postpartum (p <0.005). Mean cord blood LPV
concentration was 1.1±0.7 mg/mL and the mean ratio of
cord blood/maternal delivery LPV concentration was 0.24±0.12 (n = 15).
|
|
2nd
Trimester
|
3rd
Trimester
|
2 Weeks
Postpartum
|
|
LPV/r dose (mg)
|
400/100 twice daily
|
533/133 twice daily
|
533/133 twice daily
|
|
Mean AUC ±SD (mg*h/mL)
|
57.9 ± 21.6
|
85 ± 28.2
|
145.8 ± 50.0
|
|
Met AUC target/Total
|
5/8
|
20/23
|
17/18
|
|
Mean Cmin
± SD (mg/mL)
|
2.4 ± 1.6
|
4.5 ± 2.4
|
8.7 ± 4.5
|
Conclusions: The higher LPV/r dose (533 mg/133 mg)
provided adequate LPV exposure during the third trimester, but resulted in
excessive AUC at 2 weeks postpartum. LPV AUC was low with standard dosing (400 mg/100
mg) during the second trimester. These data suggest that the higher LPV/r dose
should be used in third trimester pregnant women, that it should be considered
in second trimester pregnant women, especially those who are protease inhibitor
experienced, and that postpartum LPV/r dosing can be reduced to standard dosing
by 2 weeks after delivery.
|
