Document Detail


Pharmacokinetics of antiretroviral drugs in anatomical sanctuary sites: the fetal compartment (placenta and amniotic fluid).
MedLine Citation:
PMID:  22155898     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
HIV resides within anatomical 'sanctuary sites' where local drug exposure and viral dynamics may differ significantly from the systemic compartment. Widespread implementation of antiretroviral therapy has seen a significant decline in the incidence of mother-to-child transmission (MTCT) of HIV. In addition to suppression of maternal plasma/genital viral loads, antiretroviral agents that cross the placenta and achieve adequate concentrations in the fetal compartment may exert a greater prophylactic effect. Penetration of antiretrovirals in the fetal compartment is expressed by accumulation ratios derived from the measurement of drug concentrations in paired maternal plasma and umbilical cord samples. The nucleoside analogues and nevirapine accumulate extensively in cord blood and in the surrounding amniotic fluid, whereas the protease inhibitors (PIs) exhibit low-to-moderate placental accumulation. Early data suggest that high placental/neonatal concentrations are achieved with raltegravir, but to a lesser extent with etravirine and maraviroc (rank order of accumulation: raltegravir/nucleoside reverse transcriptase inhibitor [tenofovir > zidovudine/lamivudine/emtricitabine/stavudine/abacavir] > non-nucleoside reverse transcriptase inhibitor [nevirapine > etravirine] > PI > maraviroc/enfuvirtide). More comprehensive in vivo pharmacokinetic data are required to justify the potential use of these agents as safe and effective options during pregnancy.
Authors:
Laura J Else; Stephen Taylor; David J Back; Saye H Khoo
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Antiviral therapy     Volume:  16     ISSN:  2040-2058     ISO Abbreviation:  Antivir. Ther. (Lond.)     Publication Date:  2011  
Date Detail:
Created Date:  2011-12-13     Completed Date:  2012-04-02     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  9815705     Medline TA:  Antivir Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  1139-47     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenine / analogs & derivatives,  pharmacokinetics,  therapeutic use
Adult
Amniotic Fluid / drug effects*,  virology
Anti-HIV Agents / pharmacokinetics*,  therapeutic use
Cyclohexanes / pharmacokinetics,  therapeutic use
Female
Fetal Blood / drug effects*,  virology
Fetus / drug effects*,  virology
HIV Envelope Protein gp41 / pharmacokinetics,  therapeutic use
HIV Fusion Inhibitors / pharmacokinetics,  therapeutic use
HIV Infections / blood,  drug therapy*,  virology
HIV Integrase Inhibitors / pharmacokinetics,  therapeutic use
HIV Protease Inhibitors / pharmacokinetics,  therapeutic use
HIV-1 / drug effects*,  physiology
Humans
Lamivudine / pharmacokinetics,  therapeutic use
Nevirapine / pharmacokinetics,  therapeutic use
Organophosphonates / pharmacokinetics,  therapeutic use
Peptide Fragments / pharmacokinetics,  therapeutic use
Placenta / drug effects*,  virology
Pregnancy
Pregnancy Complications, Infectious / prevention & control*
Pyrrolidinones / pharmacokinetics,  therapeutic use
Reverse Transcriptase Inhibitors / pharmacokinetics,  therapeutic use
Triazoles / pharmacokinetics,  therapeutic use
Viral Load / drug effects
Zidovudine / pharmacokinetics,  therapeutic use
Grant Support
ID/Acronym/Agency:
G0901364//Medical Research Council
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Cyclohexanes; 0/HIV Envelope Protein gp41; 0/HIV Fusion Inhibitors; 0/HIV Integrase Inhibitors; 0/HIV Protease Inhibitors; 0/Organophosphonates; 0/Peptide Fragments; 0/Pyrrolidinones; 0/Reverse Transcriptase Inhibitors; 0/Triazoles; 107021-12-5/tenofovir; 19OWO1T3ZE/enfuvirtide; 22VKV8053U/raltegravir; 2T8Q726O95/Lamivudine; 4B9XT59T7S/Zidovudine; 99DK7FVK1H/Nevirapine; JAC85A2161/Adenine; MD6P741W8A/maraviroc

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