Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 772-778 |
| Number of pages | 7 |
| Journal | Drug Metabolism and Disposition |
| Volume | 35 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2007 May |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pharmacology
- Toxicology
Cite this
Kinetic analysis of the transport of salicylic acid, a nonsteroidal anti-inflammatory drug, across human placenta. / Shintaku, Kyohei; Arima, Yuka; Dan, Yukihiko; Takeda, Tsutomu; Kogushi, Kentaro; Tsujimoto, Masayuki; Nagata, Hideaki; Satoh, Shoji; Tsukimori, Kiyomi; Nakano, Hitoo; Hori, Satoko; Ohtani, Hisakazu; Sawada, Yasufumi.
In: Drug Metabolism and Disposition, Vol. 35, No. 5, 05.2007, p. 772-778.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Kinetic analysis of the transport of salicylic acid, a nonsteroidal anti-inflammatory drug, across human placenta
AU - Shintaku, Kyohei
AU - Arima, Yuka
AU - Dan, Yukihiko
AU - Takeda, Tsutomu
AU - Kogushi, Kentaro
AU - Tsujimoto, Masayuki
AU - Nagata, Hideaki
AU - Satoh, Shoji
AU - Tsukimori, Kiyomi
AU - Nakano, Hitoo
AU - Hori, Satoko
AU - Ohtani, Hisakazu
AU - Sawada, Yasufumi
PY - 2007/5
Y1 - 2007/5
N2 - 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.
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.
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U2 - 10.1124/dmd.106.013029
DO - 10.1124/dmd.106.013029
M3 - Article
VL - 35
SP - 772
EP - 778
JO - Drug Metabolism and Disposition
JF - Drug Metabolism and Disposition
SN - 0090-9556
IS - 5
ER -