Population pharmacokinetics of emtricitabine in human immunodeficiency virus type 1-infected pregnant women and their neonates.
The objectives of this study were to evaluate emtricitabine (FTC) pharmacokinetics in pregnant women and their neonates and to determine the optimal prophylactic dose for neonates after birth to prevent mother-to-child transmission of human immunodeficiency virus (HIV). A total of 38 HIV-infected pregnant women were administered tenofovir disoproxyl fumarate (300 mg)-FTC (200 mg) tablets-two tablets at the initiation of labor and one daily for 7 days postpartum. By pair, 11 maternal, one cord blood, and two neonatal FTC concentrations were measured using a high-performance liquid chromatography-tandem mass spectrometry validated method and analyzed by a population approach. Model and mean estimates (interpatient variability) were a two-compartment model for mothers, with an absorption rate constant of 0.54 h(-1) (61%), apparent elimination and intercompartmental clearances of 23.2 (17%) and 6.04 liters x h(-1), and apparent central and peripheral volumes of 127 and 237 liters, respectively; an effect compartment linked to maternal circulation for cord blood and a neonatal compartment disconnected, after delivery, with a 10.6-h half-life (30%). After the 400-mg FTC administration, the median population area under the concentration-time curve and the minimal and maximal plasma FTC concentrations in pregnant women were 14.3 mg x liter(-1) x h and 1.68 and 0.076 mg/liter, respectively. At delivery, median (range) predicted maternal and cord blood FTC concentrations were, respectively, 1.16 (0.14 to 1.99) and 0.72 (0.05 to 1.19) mg x liter(-1). We concluded that the 400-mg FTC administration in pregnant women produces higher exposition than does the 200-mg administration in other adults, at steady state. FTC was shown to have good placental transfer (80%). Administering 1 mg FTC/kg as soon as possible after birth or 2 mg/kg 12 h after birth should produce neonatal concentrations comparable to the concentrations observed in adults.
Hirt
Déborah
D
EA3620, Université Paris-Descartes, Paris, France. deborah.hirt@univ-paris5.fr
Urien
Saik
S
Rey
Elisabeth
E
Arrivé
Elise
E
Ekouévi
Didier K
DK
Coffié
Patrick
P
Leang
Sim Kruy
SK
Lalsab
Sarita
S
Avit
Divine
D
Nerrienet
Eric
E
McIntyre
James
J
Blanche
Stéphane
S
Dabis
François
F
Tréluyer
Jean-Marc
JM
D000225:Adenine / Q000031:analogs & derivatives; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy; D015497:HIV-1; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn / Q000097:blood*; D008431:Maternal-Fetal Exchange / Q000187:drug effects / Q000502:physiology; D063065:Organophosphonates; D044382:Population Groups / Q000235:genetics; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood* / Q000188:drug therapy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood; D000068698:Tenofovir
D019380:Anti-HIV Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine