Abstract
The disposition of zidovudine (AZT) was investigated in near-term (day 20) pregnant rats after intravenous bolus administration of AZT at 50mg/kg. A compartmental pharmacokinetic model was developed to describe AZT concentrations in maternal plasma (1), placenta (2), fetus (3), amniotic fluid (4), and the maternal tissue compartment (5). Model equations were fitted simultaneously to all concentration data by NONLIN least-squares regression. The model that best described the AZT concentration data (F test, AIC, sum of weighted squared residuals) incorporated bidirectional transfer between maternal plasma ⇌ placenta, placenta ⇌ fetus, placenta ⇌ amniotic fluid, and maternal plasma ⇌ tissue compartment. Transfer rate constants (1/h) were as follows: k12, 0.58 ±0.41; k21, 47.64±46.61; k23, 67.50±42.03; k32, 13.09±8.80; k24, 0.62±0.03; k42, 0.32±0.06; k15, 5.75±7.00; k51, 4.12±1.01; and k10, 1.51±0.80. AZT rapidly distributed into tissue and placenta compartments. However, AZT accumulated more slowly into amniotic fluid. Intercompartmental distributional clearances suggest that the mechanism of maternal–placental, placental–fetal, and fetal–amniotic fluid transfer of AZT was by passive diffusion. This maternal–fetal model for AZT may offer a useful approach for describing the placental transfer kinetics of other antiviral nucleosides as well.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
