Impact of body weight and missed doses on lopinavir concentrations with standard and increased lopinavir/ritonavir doses during late pregnancy

J Antimicrob Chemother. 2015 Jan;70(1):217-24. doi: 10.1093/jac/dku367. Epub 2014 Sep 25.

Abstract

Objectives: To assess the influence of body weight and missed doses on lopinavir pharmacokinetics with standard and increased doses of lopinavir/ritonavir melt extrusion tablets during late pregnancy.

Patients and methods: Lopinavir concentration data during the third trimester of pregnancy were pooled from clinical trials in Thailand (NCT00409591) and the USA (NCT00042289). A total of 154 HIV-infected pregnant women receiving either 400/100 mg (standard) or 600/150 mg (increased) twice daily had lopinavir plasma concentration data available. Population parameters were estimated using non-linear mixed-effects regression models. Monte Carlo simulations were performed to estimate the probability of achieving target lopinavir trough concentrations (>1.0 mg/L) with standard and increased doses of lopinavir/ritonavir during pregnancy.

Results: The median (range) age, weight and gestational age were 28 years (18-43), 62 kg (45-123) and 33 weeks (29-38), respectively. Body weight influenced lopinavir oral clearance (CL/F) and volume of distribution (V/F). Population estimates of lopinavir CL/F and V/F were 6.21 L/h/70 kg and 52.6 L/70 kg, respectively. Based on simulations, the highest risk of subtherapeutic trough concentrations was for women weighing >100 kg using the standard dose (∼ 7%), while the risk was <2% with the 600/150 mg dose for women weighing 40-130 kg. After a missed dose, 61% of women have lopinavir concentrations below target prior to the next dose with the standard dose compared with 42% with the increased dose.

Conclusions: Standard dosing provides adequate lopinavir trough concentrations for the majority of pregnant women but increased doses may be preferable for women weighing >100 kg and with a history of lopinavir/ritonavir use and/or adherence issues.

Keywords: HIV; Thailand; USA; pharmacokinetics.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / pharmacokinetics
  • Body Weight
  • Clinical Trials as Topic
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Infectious Disease Transmission, Vertical / prevention & control*
  • Lopinavir / administration & dosage*
  • Lopinavir / pharmacokinetics
  • Monte Carlo Method
  • Plasma / chemistry
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy*
  • Prospective Studies
  • Ritonavir / administration & dosage*
  • Ritonavir / pharmacokinetics
  • Thailand
  • Treatment Outcome
  • United States
  • Young Adult

Substances

  • Anti-HIV Agents
  • Lopinavir
  • Ritonavir