RT Journal Article
SR Electronic
T1 Kinetic Analysis of the Transport of Salicylic Acid, a Nonsteroidal Anti-inflammatory Drug, across Human Placenta
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 772
OP 778
DO 10.1124/dmd.106.013029
VO 35
IS 5
A1 Kyohei Shintaku
A1 Yuka Arima
A1 Yukihiko Dan
A1 Tsutomu Takeda
A1 Kentaro Kogushi
A1 Masayuki Tsujimoto
A1 Hideaki Nagata
A1 Shoji Satoh
A1 Kiyomi Tsukimori
A1 Hitoo Nakano
A1 Satoko Hori
A1 Hisakazu Ohtani
A1 Yasufumi Sawada
YR 2007
UL http://dmd.aspetjournals.org/content/35/5/772.abstract
AB The aim of this study was to develop a pharmacokinetic model to describe the transplacental transfer of drugs, based on the human placental perfusion study. The maternal and fetal sides of human placentas were perfused with salicylic acid together with antipyrine, a passive diffusion marker. The drug concentration in the placental tissue was determined at the end of perfusion. A compartment model consisting of maternal space, fetal intravascular space, and placental tissue was fitted to the observed concentration profiles of salicylic acid in the maternal and fetal effluents. The developed model could adequately explain the concentration profiles of salicylic acid in the effluents with influx clearances from maternal and fetal perfusates to placental tissue of 0.0407 and 0.0813 ml/min/g cotyledon and efflux rate constants from placental tissue to maternal and fetal perfusates (k2 and k3) of 0.0238 and 0.176 min–1, respectively. The kinetics of antipyrine was adequately described by assuming rapid equilibrium between fetal perfusate and placental tissue compartments. The influx plasma clearance from the maternal side (K″1) in humans was estimated by taking into account the protein binding. The K″1/k2 value of salicylic acid was 1.07 ml/g cotyledon and was larger than that of antipyrine (0.642 ml/g cotyledon). We evaluated the transplacental transfer kinetics of salicylic acid by human placental perfusion study with various perfusion protocols. Based on the data obtained, we developed a pharmacokinetic model, which should enable us to estimate the influx profile of drugs into umbilical arterial blood from the maternal plasma concentration profile. The American Society for Pharmacology and Experimental Therapeutics