title: Impact of body weight and missed doses on lopinavir concentrations with standard and increased lopinavir/ritonavir doses during late pregnancy.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Program for HIV Prevention and Treatment (IRD UMI 174), Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand Harvard School of Public Health, Boston, MA, USA Institut de Recherché pour le Développement (IRD), UMI 174-PHPT, Marseille, France tim.cressey@phpt.org.
authors.forename: Tim R
authors.initials: TR
authors.lastname: Cressey
authors.affiliation: EA-3620 University Paris Descartes and CIC-0901 Inserm, Paris, France Hôpital Cochin, Assistance Publique-Hopitaux de Paris, Paris, France Unité de Recherche clinique, AP-HP, Hôpital Tarnier, Paris, France.
authors.forename: Saik
authors.initials: S
authors.lastname: Urien
authors.affiliation: University of California San Diego, La Jolla, CA, USA.
authors.forename: Edmund V
authors.initials: EV
authors.lastname: Capparelli
authors.affiliation: University of California San Diego, La Jolla, CA, USA.
authors.forename: Brookie M
authors.initials: BM
authors.lastname: Best
authors.affiliation: Mae Chan Hospital, Mae Chan, Thailand.
authors.forename: Sudanee
authors.initials: S
authors.lastname: Buranabanjasatean
authors.affiliation: Nakornping Hospital, Chiang Mai, Thailand.
authors.forename: Aram
authors.initials: A
authors.lastname: Limtrakul
authors.affiliation: Nopparat Rajathanee Hospital, Bangkok, Thailand.
authors.forename: Boonsong
authors.initials: B
authors.lastname: Rawangban
authors.affiliation: Samutprakarn Hospital, Samutprakarn, Thailand.
authors.forename: Prapan
authors.initials: P
authors.lastname: Sabsanong
authors.affiliation: EA-3620 University Paris Descartes and CIC-0901 Inserm, Paris, France Hôpital Cochin, Assistance Publique-Hopitaux de Paris, Paris, France Unité de Recherche clinique, AP-HP, Hôpital Tarnier, Paris, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Treluyer
authors.affiliation: Program for HIV Prevention and Treatment (IRD UMI 174), Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand Harvard School of Public Health, Boston, MA, USA Institut de Recherché pour le Développement (IRD), UMI 174-PHPT, Marseille, France.
authors.forename: Gonzague
authors.initials: G
authors.lastname: Jourdain
authors.affiliation: University of Southern California, Los Angeles, CA, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Stek
authors.affiliation: Program for HIV Prevention and Treatment (IRD UMI 174), Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand Harvard School of Public Health, Boston, MA, USA Institut de Recherché pour le Développement (IRD), UMI 174-PHPT, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lallemant
authors.affiliation: Boston University, Boston, MA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Mirochnick
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001835:Body Weight; D002986:Clinical Trials as Topic; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D061466:Lopinavir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009010:Monte Carlo Method; D010949:Plasma / Q000737:chemistry; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011446:Prospective Studies; D019438:Ritonavir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013785:Thailand; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D061466:Lopinavir; D019438:Ritonavir
keywords: HIV; Thailand; USA; pharmacokinetics