Kinetic analysis of the transport of salicylic acid, a nonsteroidal anti-inflammatory drug, across human placenta

Kyohei Shintaku, Yuka Arima, Yukihiko Dan, Tsutomu Takeda, Kentaro Kogushi, Masayuki Tsujimoto, Hideaki Nagata, Shoji Satoh, Kiyomi Tsukimori, Hitoo Nakano, Satoko Hori, Hisakazu Ohtani, Yasufumi Sawada

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 languageEnglish
Pages (from-to)772-778
Number of pages7
JournalDrug Metabolism and Disposition
Volume35
Issue number5
DOIs
Publication statusPublished - 2007 May
Externally publishedYes

Fingerprint

Salicylic Acid
Placenta
Anti-Inflammatory Agents
Antipyrine
Mothers
Tissue
Kinetics
Cotyledon
Pharmacokinetics
Pharmaceutical Preparations
Perfusion
Effluents
Plasmas
Umbilicus
Rate constants
Blood
Protein Binding

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 journalArticle

Shintaku, K, Arima, Y, Dan, Y, Takeda, T, Kogushi, K, Tsujimoto, M, Nagata, H, Satoh, S, Tsukimori, K, Nakano, H, Hori, S, Ohtani, H & Sawada, Y 2007, 'Kinetic analysis of the transport of salicylic acid, a nonsteroidal anti-inflammatory drug, across human placenta', Drug Metabolism and Disposition, vol. 35, no. 5, pp. 772-778. https://doi.org/10.1124/dmd.106.013029
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. / Kinetic analysis of the transport of salicylic acid, a nonsteroidal anti-inflammatory drug, across human placenta. In: Drug Metabolism and Disposition. 2007 ; Vol. 35, No. 5. pp. 772-778.
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AU - Kogushi, Kentaro

AU - Tsujimoto, Masayuki

AU - Nagata, Hideaki

AU - Satoh, Shoji

AU - Tsukimori, Kiyomi

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