Document Detail


Protein binding of lopinavir and ritonavir during 4 phases of pregnancy: implications for treatment guidelines.
MedLine Citation:
PMID:  23221983     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To investigate the intraindividual pharmacokinetics (PKs) of total (protein bound plus unbound) and unbound lopinavir/ritonavir (LPV/RTV) and to assess whether the pediatric formulation (100 mg/25 mg) can overcome any pregnancy-associated changes.
DESIGN: Prospective longitudinal PK study.
METHODS: HIV-infected pregnant antiretroviral therapy-naive and experienced women receiving LPV/RTV 400 mg/100 mg tablets twice daily. Intensive PK evaluations were performed at 20-24 weeks (PK1), 30 weeks (PK2) followed by empiric dose increase using the pediatric formulation (100 mg/25 mg twice daily), 32 weeks (PK3), and 8 weeks postpartum (PK4).
RESULTS: Twelve women completed prespecified PK evaluations. Median (range) age was 28 (18-35) years and baseline BMI was 32 (19-41) kg/m. During pregnancy, total area under the time concentration (AUC0-12h) for LPV was significantly lower than postpartum (PK1, PK2, or PK3 vs. PK4, P = 0.005). Protein-unbound LPV AUC0-12h remained unchanged during pregnancy [PK1: 1.6 (1.3-1.9) vs. PK2: 1.6 (1.3-1.9) μg·h/mL, P = 0.4] despite a 25% dose increase [PK2 vs. PK3: 1.8 (1.3-2.1) μg·h/mL, P = 0.5]. Protein-unbound LPV predose concentrations (C12h) did not significantly change despite dose increase [PK2: 0.10 (0.08-0.15) vs. PK3: 0.12 (0.10-0.15) μg/mL, P = 0.09]. Albumin and LPV AUC0-12h fraction unbound were correlated (rs = 0.3, P = 0.03).
CONCLUSIONS: Total LPV exposure was significantly decreased throughout pregnancy despite the increased dose. However, the exposure of unbound LPV did not change significantly regardless of trimester or dose. Predose concentrations of unbound LPV were not affected by the additional dose and were 70-fold greater than the minimum efficacy concentration. These findings suggest dose adjustments may not be necessary in all HIV-infected pregnant women.
Authors:
Kristine B Patterson; Julie B Dumond; Heather A Prince; Amanda J Jenkins; Kimberly K Scarsi; Ruili Wang; Stephanie Malone; Michael G Hudgens; Angela D M Kashuba
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of acquired immune deficiency syndromes (1999)     Volume:  63     ISSN:  1944-7884     ISO Abbreviation:  J. Acquir. Immune Defic. Syndr.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-11     Completed Date:  2013-06-24     Revised Date:  2014-10-09    
Medline Journal Info:
Nlm Unique ID:  100892005     Medline TA:  J Acquir Immune Defic Syndr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  51-8     Citation Subset:  IM; X    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Blood Proteins / metabolism
Female
HIV Infections / drug therapy*,  virology
HIV Protease Inhibitors / administration & dosage,  pharmacokinetics*,  therapeutic use
Humans
Lopinavir / administration & dosage,  metabolism,  pharmacokinetics*,  therapeutic use
Pregnancy
Pregnancy Complications, Infectious / drug therapy*,  virology
Pregnancy Trimesters
Prospective Studies
Protein Binding
Ritonavir / administration & dosage,  pharmacokinetics*,  therapeutic use
Young Adult
Grant Support
ID/Acronym/Agency:
K23 AI054980/AI/NIAID NIH HHS; K23 AI077355/AI/NIAID NIH HHS; K23 AI093156/AI/NIAID NIH HHS; K23 AI54980/AI/NIAID NIH HHS; K23 AI77355/AI/NIAID NIH HHS; P30 AI050410/AI/NIAID NIH HHS; P30 AI50410/AI/NIAID NIH HHS; R34 AI087065/AI/NIAID NIH HHS; R34 AI087065/AI/NIAID NIH HHS; UL1 RR025741/RR/NCRR NIH HHS; UL1 RR025741/RR/NCRR NIH HHS; UL1 RR025747/RR/NCRR NIH HHS; UL1 RR025747/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Blood Proteins; 0/HIV Protease Inhibitors; 2494G1JF75/Lopinavir; O3J8G9O825/Ritonavir
Comments/Corrections
Comment In:
J Acquir Immune Defic Syndr. 2014 Jul 1;66(3):e64-5   [PMID:  24694928 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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