Document Detail

Protein Binding of Lopinavir and Ritonavir During Four Phases of Pregnancy: Implications for Treatment Guidelines.
MedLine Citation:
PMID:  23221983     Owner:  NLM     Status:  Publisher    
OBJECTIVE:: To investigate the intraindividual pharmacokinetics of total (protein bound + unbound) and unbound lopinavir/ritonavir (LPV/RTV) and to assess whether the pediatric formulation (100mg/25mg) can overcome any pregnancy-associated changes. Design: Prospective longitudinal pharmacokinetic (PK) study METHODS:: HIV-infected pregnant antiretroviral therapy-naïve and experienced women receiving LPV/RTV 400mg/100mg 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 (100mg/25mg twice daily), 32 weeks (PK3), and 8 weeks postpartum (PK4). RESULTS:: Twelve women completed pre-specified 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 (AUC0-12hr) for LPV was significantly lower than postpartum [PK1, PK2 or PK3 vs. PK4, p= 0.005]. Protein unbound LPV AUC0-12hr remained unchanged during pregnancy [PK1: 1.6 (1.3-1.9) vs. PK2: 1.6 (1.3-1.9) μg*hr/mL, p=0.4] despite a 25% dose increase [PK2 vs. PK3: 1.8 (1.3-2.1) μg*hr/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.
Kristine B Patterson; Julie B Dumond; Heather A Prince; Amanda J Jenkins; Kimberly K Scarsi; Ruili Wang; Stephanie Malone; Michael G Hudgens; Angela Kashuba
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-6
Journal Detail:
Title:  Journal of acquired immune deficiency syndromes (1999)     Volume:  -     ISSN:  1944-7884     ISO Abbreviation:  J. Acquir. Immune Defic. Syndr.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100892005     Medline TA:  J Acquir Immune Defic Syndr     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1University of North Carolina Department of Medicine, Chapel Hill, NC 2University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC 3Northwestern University Feinberg School of Medicine, Chicago, IL *Current affiliation: United Therapeutics, Research Triangle Park, NC.
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