Kinetic analysis of the transport of salicylic acid, a nonsteroidal anti-inflammatory drug, across human placenta
| Autor: | Yuka Arima, Hitoo Nakano, Kentaro Kogushi, Hideaki Nagata, Yasufumi Sawada, Hisakazu Ohtani, Shoji Satoh, Satoko Hori, Kiyomi Tsukimori, Kyohei Shintaku, Masayuki Tsujimoto, Tsutomu Takeda, Yukihiko Dan |
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| Rok vydání: | 2007 |
| Předmět: |
Time Factors
Placenta Pharmaceutical Science Pharmacology Models Biological Permeability chemistry.chemical_compound Pharmacokinetics Fetal membrane Pregnancy medicine Humans Fetus biology Chemistry Anti-Inflammatory Agents Non-Steroidal Transplacental Perfusion Kinetics medicine.anatomical_structure Enzyme inhibitor biology.protein Female Salicylic Acid Salicylic acid Algorithms Antipyrine |
| Zdroj: | Drug metabolism and disposition: the biological fate of chemicals. 35(5) |
| ISSN: | 0090-9556 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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