Raltegravir pharmacokinetics during pregnancy

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Maternal-Fetal Medicine
• Infectious Diseases

Background:

• Antiretroviral therapy is crucial for managing HIV in pregnant women.
• Understanding drug pharmacokinetics (PK) during pregnancy is essential for optimizing treatment efficacy and safety.
• Raltegravir is an integrase inhibitor used in combination antiretroviral therapy.

Purpose of the Study:

• To evaluate the pharmacokinetics (PK) of raltegravir in HIV-infected women during pregnancy and postpartum.
• To assess raltegravir exposure and trough concentrations in relation to established targets.
• To determine raltegravir transfer across the placenta.

Main Methods:

• Prospective study (NCT00042289) involving HIV-infected women on combination antiretroviral therapy including raltegravir (400 mg twice daily).
• Intensive 12-hour PK profiles were obtained during the second and third trimesters and 6-12 weeks postpartum.
• Trough concentrations were compared to a target of 0.035 microg/mL.

Main Results:

• Median raltegravir area under the curve (AUC) was significantly reduced during pregnancy (5.4–6.6 microg·h/mL) compared to postpartum (11.6 microg·h/mL).
• Trough concentrations were below target in a notable proportion of women during late pregnancy and postpartum (21-31%).
• Raltegravir readily crossed the placenta, with a median cord blood/maternal concentration ratio of 1.5; 92% of women achieved viral suppression at delivery.

Conclusions:

• Raltegravir exposure is reduced by approximately 50% during pregnancy, with frequent sub-target trough concentrations.
• Raltegravir effectively crosses the placenta.
• Despite reduced exposure, current raltegravir dosing appears adequate for maintaining viral suppression in HIV-infected pregnant women.