Transfer of acipimox across the isolated perfused human placenta.
The placental transfer of the new lipid-lowering agent, acipimox was investigated in the isolated perfused human placenta. Placentas obtained at caesarean section were perfused for 120 min, with both maternal and fetal circuits in closed recycling mode. Acipimox was added to either the maternal circuit alone (five experiments) or to both maternal and fetal circuits simultaneously (five experiments) to achieve initial concentrations of 5 micrograms/ml. Antipyrine (20 micrograms/ml) and l-(14C)-leucine (250 microM) were added in like fashion as reference compounds. Two hours after addition to the maternal circuit alone antipyrine was close to equilibrium across the placenta, but equilibration of acipimox was incomplete (fetal/maternal ratio = 0.58 +/- 0.11). Maternal to fetal placental clearance of acipimox (0.80 +/- 0.18 ml/min) was 25 per cent of antipyrine clearance. After simultaneous administration to both maternal and fetal circuits the l-(14C)-leucine fetal/maternal ratio was 1.44 +/- 0.13 at 120 min, whereas maternal and fetal concentrations of acipimox and antipyrine were at equilibrium for the duration of the experiment (fetal/maternal ratio of acipimox at 120 min = 1.10 +/- 0.06). This study shows that acipimox is transferred across the human placenta by diffusion at a slow rate. The low permeability of the placenta may afford some protection to the fetus from acipimox administered to the mother in vivo.
Ghabrial
H
H
University of Melbourne, Department of Medicine, Melbourne, Victoria, Australia.
Czuba
M A
MA
Stead
C K
CK
Smallwood
R A
RA
Morgan
D J
DJ
D000983:Antipyrine / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007930:Leucine / Q000493:pharmacokinetics; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000502:physiology*; D011247:Pregnancy; D011719:Pyrazines / Q000493:pharmacokinetics*
D000960:Hypolipidemic Agents; D011719:Pyrazines; D007930:Leucine; C027696:acipimox; D000983:Antipyrine