Transfer of meropenem in the ex vivo human placenta perfusion model.
OBJECTIVE
To determine maternal-fetal transplacental passage of meropenem in the ex vivo human perfusion model.


METHODS
Term placentae (n = 6) were collected immediately after delivery. A single cotyledon was localized, perfused and stabilized with physiologic Eagles minimal essential medium containing 3% bovine albumin and heparin as described by Chalier (Chalier JC. Criteria for evaluating perfusion experiments and presentation results. Contrib Gynecol Obstet 1985; 13:32 - 39). Meropenem was added to the maternal medium in concentrations similar to maternal serum peak and trough levels, then perfused through the maternal circulation of the cotyledon. To assess transfer and accumulation, fluid aliquots from both the maternal and fetal compartments were collected over an hour at defined intervals in an open and closed system. Antipyrine 14C was added to the medium in order to calculate the transport fraction and clearance indexes. Meropenem and antipyrine 14C concentrations were determined by High-pressure Liquid Chromatography and liquid scintillation, respectively.


RESULTS
Mean antipyrine transport fraction was 2.33 + 0.25. Maternal and fetal mean meropenem peak concentrations were 54.3 + 3.3 microg/ml and 2.2 + 0.18 microg/ml, respectively. Whereas, maternal and fetal mean trough concentrations were 12.7 + 1.3 microg/ml and 0.41 + 0.10 microg/ml, respectively. Mean peak clearance index was 0.077 + 0.007 and the mean trough was 0.052 + 0.015. Mean accumulation for the peak and trough concentrations of meropenem were 0.9 and 2.95 microg/ml, respectively.


CONCLUSIONS
Transplacental passage of meropenem was incomplete in the ex vivo human placental perfusion model. Accumulation was also noted in the fetal compartment.
Hnat
Michael
M
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, The University of Texas, Southwestern Medical Center, Dallas, TX 75390-9032, USA.
Bawdon
Roger E
RE
D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D000077731:Meropenem; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D013845:Thienamycins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000890:Anti-Infective Agents; D013845:Thienamycins; D000077731:Meropenem