title: Pharmacokinetics of antiretroviral drugs in anatomical sanctuary sites: the fetal compartment (placenta and amniotic fluid).
abstract: 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.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK. l.j.else@liv.ac.uk
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Else
authors.forename: Stephen
authors.initials: S
authors.lastname: Taylor
authors.forename: David J
authors.initials: DJ
authors.lastname: Back
authors.forename: Saye H
authors.initials: SH
authors.lastname: Khoo
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D000328:Adult; D000653:Amniotic Fluid / Q000187:drug effects* / Q000821:virology; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003510:Cyclohexanes / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077560:Enfuvirtide; D005260:Female; D005312:Fetal Blood / Q000187:drug effects* / Q000821:virology; D005333:Fetus / Q000187:drug effects* / Q000821:virology; D015700:HIV Envelope Protein gp41 / Q000493:pharmacokinetics / Q000627:therapeutic use; D023581:HIV Fusion Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D019428:HIV Integrase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019259:Lamivudine / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077592:Maraviroc; D019829:Nevirapine / Q000493:pharmacokinetics / Q000627:therapeutic use; D063065:Organophosphonates / Q000493:pharmacokinetics / Q000627:therapeutic use; D010446:Peptide Fragments / Q000493:pharmacokinetics / Q000627:therapeutic use; D010920:Placenta / Q000187:drug effects* / Q000821:virology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000517:prevention & control*; D011760:Pyrrolidinones / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068698:Tenofovir; D014230:Triazoles / Q000493:pharmacokinetics / Q000627:therapeutic use; D019562:Viral Load / Q000187:drug effects; D015215:Zidovudine / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D003510:Cyclohexanes; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D063065:Organophosphonates; D010446:Peptide Fragments; D011760:Pyrrolidinones; D018894:Reverse Transcriptase Inhibitors; D014230:Triazoles; D000077560:Enfuvirtide; D019259:Lamivudine; D000068898:Raltegravir Potassium; D015215:Zidovudine; D019829:Nevirapine; D000068698:Tenofovir; D000225:Adenine; D000077592:Maraviroc