Lopinavir tablet pharmacokinetics with an increased dose during pregnancy

J Acquir Immune Defic Syndr. 2010 Aug;54(4):381-8. doi: 10.1097/qai.0b013e3181d6c9ed.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacokinetics*
  • Anti-HIV Agents / therapeutic use
  • Area Under Curve
  • Body Weight
  • Cohort Studies
  • Continental Population Groups
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Ethnic Groups
  • Female
  • Gestational Age
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • Humans
  • Lopinavir
  • Postpartum Period / drug effects
  • Postpartum Period / physiology
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Pregnancy Complications / virology*
  • Pregnancy Trimester, Second
  • Pregnancy Trimester, Third
  • Pyrimidinones / pharmacokinetics*
  • Pyrimidinones / therapeutic use
  • Zidovudine / therapeutic use

Substances

  • Anti-HIV Agents
  • Pyrimidinones
  • Lopinavir
  • Zidovudine