Total, unbound, renal and hepatic clearances of raltegravir and the formation and elimination clearances of raltegravir glucuronide in pregnant women.

This work aimed to evaluate the total, unbound, renal and hepatic clearances of raltegravir (RAL) and the formation and elimination clearances of raltegravir glucuronide (RAL GLU) in pregnant women living with HIV. The participants received raltegravir 400 mg twice daily during the third trimester (n = 15) of gestation, delivery (n = 15), and the postpartum period (n = 8). Pharmacokinetic parameter values were calculated based on plasma and urine data using noncompartmental methods. RAL clearances for the third trimester of gestation were as follows [geometric means (95% CI)] total clearance: 63.63 L/h (47.5-85.25); renal clearance: 2.56 L/h (1.96-3.34); hepatic clearance: 60.52 L/h (44.65-82.04), and unbound clearance: 281.14 L/h (203.68-388.05). RAL GLU formation and elimination clearances for the third trimester of gestation were 7.57 (4.94 -11.6) and 8.71 (6.71-11.32) L/h, respectively. No differences were observed in RAL GLU pharmacokinetic parameters between the third trimester of gestation and the postpartum period, except for higher formation (7.57 vs. 4.03 L/h) and elimination (8.71 vs. 4.92 L/h) clearances during the third trimester. The findings based on plasma and urine data are consistent with an increase in the hepatic UGT isoenzymes activities involved in RAL metabolism during pregnancy, and the formation of RAL GLU is a minor route of RAL elimination. Compared to the postpartum period, in the third trimester of gestation, the similar RAL plasma exposure in pregnant women reinforces the maintenance of a RAL regimen including a 400-mg oral dose twice daily during pregnancy. This article is protected by copyright. All rights reserved.