AIMS: A population pharmacokinetic model was developed to characterize the transfer of nelfinavir and its active metabolite M8 from maternal to cord plasma and amniotic fluid. METHODS: Concentration data were obtained from 75 women on the day of delivery and for whom maternal, umbilical plasma and amniotic fluid samples were collected. Data from 53 pregnant, 61 nonpregnant and seven consecutively pregnant and non pregnant women were then added to the database, the contents of which were analyzed using NONMEM. RESULTS: Nelfinavir and M8 concentrations in maternal plasma, umbilical plasma and amniotic fluid were described by six connected compartments. Mean (% intersubject variability) population estimates were: absorption rate 00.67 h(-1), lag time 00.87 h, oral clearance and volume of distribution: 39.5 l h(-1) (53%), and 557 l for non pregnant and pregnant women, respectively, and 115 l h(-1) (132%) and 1626 l, respectively, on the day of delivery, M8 formation clearance 0.77 l h(-1) and M8 elimination rate constant 03.41 h(-1) (74%). For nelfinavir and M8, respectively, the mother-to-cord parameters were 0.058 l h(-1) (34%), and 00.35 h(-1) (76%), the cord-to-amniotic fluid rate constants were 0.23 and 00.59 h(-1), and the elimination rate constants from amniotic fluid were 0.36 and 00.49 h(-1). The nelfinavir fetus : maternal concentration ratio was 25% for maternal concentrations between 0.1 and 2.5 mg l(-1), between the 31 and 41st week of gestation. CONCLUSIONS: The low transfer of nelfinavir from the placenta is unlikely to protect the fetus from vertical HIV-1 transmission.
AIMS: A population pharmacokinetic model was developed to characterize the transfer of nelfinavir and its active metabolite M8 from maternal to cord plasma and amniotic fluid. METHODS: Concentration data were obtained from 75 women on the day of delivery and for whom maternal, umbilical plasma and amniotic fluid samples were collected. Data from 53 pregnant, 61 nonpregnant and seven consecutively pregnant and non pregnant women were then added to the database, the contents of which were analyzed using NONMEM. RESULTS:Nelfinavir and M8 concentrations in maternal plasma, umbilical plasma and amniotic fluid were described by six connected compartments. Mean (% intersubject variability) population estimates were: absorption rate 00.67 h(-1), lag time 00.87 h, oral clearance and volume of distribution: 39.5 l h(-1) (53%), and 557 l for non pregnant and pregnant women, respectively, and 115 l h(-1) (132%) and 1626 l, respectively, on the day of delivery, M8 formation clearance 0.77 l h(-1) and M8 elimination rate constant 03.41 h(-1) (74%). For nelfinavir and M8, respectively, the mother-to-cord parameters were 0.058 l h(-1) (34%), and 00.35 h(-1) (76%), the cord-to-amniotic fluid rate constants were 0.23 and 00.59 h(-1), and the elimination rate constants from amniotic fluid were 0.36 and 00.49 h(-1). The nelfinavir fetus : maternal concentration ratio was 25% for maternal concentrations between 0.1 and 2.5 mg l(-1), between the 31 and 41st week of gestation. CONCLUSIONS: The low transfer of nelfinavir from the placenta is unlikely to protect the fetus from vertical HIV-1 transmission.
Authors: Mark Mirochnick; Alex Dorenbaum; Diane Holland; Bethann Cunningham-Schrader; Colleen Cunningham; Richard Gelber; Lynne Mofenson; Mary Culnane; James Connor; John L Sullivan Journal: Pediatr Infect Dis J Date: 2002-09 Impact factor: 2.129
Authors: L Mandelbrot; A Landreau-Mascaro; C Rekacewicz; A Berrebi; J L Bénifla; M Burgard; E Lachassine; B Barret; M L Chaix; A Bongain; N Ciraru-Vigneron; C Crenn-Hébert; J F Delfraissy; C Rouzioux; M J Mayaux; S Blanche Journal: JAMA Date: 2001-04-25 Impact factor: 56.272
Authors: K E Zhang; E Wu; A K Patick; B Kerr; M Zorbas; A Lankford; T Kobayashi; Y Maeda; B Shetty; S Webber Journal: Antimicrob Agents Chemother Date: 2001-04 Impact factor: 5.191
Authors: David M Burger; Alina S Bergshoeff; Ronald De Groot; Diana Gibb; Sarah Walker; Jean-Marc Tréluyer; Richard M W Hoetelmans Journal: J Pediatr Date: 2004-09 Impact factor: 4.406
Authors: Sarah K Himes; Karl B Scheidweiler; Katherine Tassiopoulos; Deborah Kacanek; Rohan Hazra; Kenneth Rich; Marilyn A Huestis Journal: Anal Chem Date: 2013-01-14 Impact factor: 6.986
Authors: Ahizechukwu C Eke; Adeniyi Olagunju; Brookie M Best; Mark Mirochnick; Jeremiah D Momper; Elaine Abrams; Martina Penazzato; Tim R Cressey; Angela Colbers Journal: Clin Pharmacokinet Date: 2020-10 Impact factor: 6.447