Lopinavir tablet pharmacokinetics with an increased dose during pregnancy

Abstract

Objective: Reduced lopinavir concentrations have been demonstrated with use of the capsule formulation during the third trimester of pregnancy. This study determined lopinavir exposure with an increased dose of the new tablet formulation during the third trimester.

Design: International Maternal Pediatric Adolescent AIDS Clinical Trials 1026s is a prospective nonblinded pharmacokinetic study in HIV-infected pregnant women, including a cohort receiving 2 lopinavir/ritonavir tablets (400 mg/100 mg) twice daily during the second trimester, 3 tablets (600 mg/150 mg) twice daily during the third trimester, and 2 tablets (400 mg/100 mg) twice daily post delivery through 2 weeks postpartum.

Methods: Steady-state 12-hour pharmacokinetic profiles were performed during pregnancy and at 2 weeks postpartum. Lopinavir and ritonavir were measured by reverse-phase high-performance liquid chromatography (detection limit, 0.09 mcg/mL).

Results: Thirty-three women were studied. Median lopinavir AUC for the second trimester (n = 11), third trimester (n = 33), and postpartum (n = 27) were 72, 96, and 133 mcg x hr/mL, respectively. Median minimum lopinavir concentrations were 3.4, 4.9, and 6.9 mcg/mL.

Conclusions: The higher lopinavir/ritonavir tablet dose (600 mg/150 mg) provided exposure during the third trimester similar to the average AUC (98 mcg x hr x mL(-1) in nonpregnant adults taking 400 mg/100 mg twice daily. The higher dose should be used during the second and third trimesters of pregnancy. Postpartum dosing can be reduced to standard dosing before 2 weeks postpartum.

FIGURE 1

Median lopinavir concentrations during second trimester, third trimester, and postpartum. Median lopinavir concentration–time curves ± interquartile range during the second trimester (long dashed line, n = 11), third trimester (medium dashed line, n = 33), and postpartum (fine dashed line, n = 27). The solid line represents the expected (50th percentile) concentration–time profile in nonpregnant adults.

FIGURE 2

Lopinavir AUC second trimester, third trimester, and postpartum. Changes in lopinavir area under the concentration–time curves from the second trimester to the third trimester to postpartum (n = 27). The solid line indicates typical value (50th percentile) AUC of tablets in nonpregnant adults of 93 mcg·hr/mL.