title: Long-term administration of tenofovir or emtricitabine to pregnant rats; effect on Abcb1a, Abcb1b and Abcg2 expression in the placenta and in maternal and fetal organs.
abstract: OBJECTIVE
  Tenofovir and emtricitabine are very effective and well-tolerated antiretrovirals representing current backbone of the antiretroviral combination regimens for the prevention of perinatal HIV transmission. The aim of our study was to determine whether tenofovir or emtricitabine administered in long-term fashion affect expression of two widely described pharmacokinetic determinants, P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), in maternal or fetal biological tissues.
  
  
  METHODS
  For this purpose, pregnant Wistar rats were administered tenofovir (2.25 mg/kg/day), emtricitabine (3.5 mg/kg/day) or saline i.m. for 10 days (from the 12th to 21st gestation day). On the 22nd day, the placenta and maternal/fetal intestine, brain, kidneys and liver were sampled and analysed for Abcb1a, Abcb1b and Abcg2 expression; placental and newborns' weights were also monitored.
  
  
  RESULTS
  We found that long-term application of tenofovir or emtricitabine did not significantly affect expression of Abcb1a, Abcb1b and Abcg2 in either maternal or fetal organs. However, tenofovir administration significantly increased placenta-to-birthweight ratio, a strong indicator of various diseases occurring later in life.
  
  
  CONCLUSIONS
  Our data broaden current knowledge on safety profile of tenofovir and emtricitabine use in pregnancy. Nevertheless, further research in other mammal species, including humans, is important to fully elucidate this issue.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic.
authors.forename: Lukas
authors.initials: L
authors.lastname: Cerveny
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Neumanova
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic.
authors.forename: Sara
authors.initials: S
authors.lastname: Karbanova
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic.
authors.forename: Ivana
authors.initials: I
authors.lastname: Havlova
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic.
authors.forename: Frantisek
authors.initials: F
authors.lastname: Staud
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D000068679:Emtricitabine / Q000008:administration & dosage*; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D000068698:Tenofovir / Q000008:administration & dosage*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C489249:Abcg2 protein, rat; D000068698:Tenofovir; C095122:multidrug resistance protein 3; D000068679:Emtricitabine
keywords: ABC transporters; drug interactions; emtricitabine; pregnancy; tenofovir