Transplacental pharmacokinetics of diclofenac in perfused human placenta.

Kyohei Shintaku, Satoko Hori, Masayuki Tsujimoto, Hideaki Nagata, Shoji Satoh, Kiyomi Tsukimori, Hitoo Nakano, Tomoyuki Fujii, Yuji Taketani, Hisakazu Ohtani, Yasufumi Sawada

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11 Citations (Scopus)

Abstract

The aims of this study were to evaluate the transplacental transfer properties of diclofenac and to determine the effect of L-lactic acid on the transplacental transfer of diclofenac. The maternal and fetal vessels of human placenta were perfused in a single-pass mode with a solution containing diclofenac and antipyrine. The transplacental pharmacokinetic model was fitted to the time profiles of the drug concentrations in the effluent and placenta to obtain transplacental pharmacokinetic parameters. In addition, chloride ion in the perfusate was partially replaced with L-lactic acid to see the change in the transplacental transfer properties of diclofenac. The TPT(ss) value (ratio of the rate of amount transferred across the placenta to that infused in the steady state) of diclofenac was 2.22%, which was approximately one-third that of antipyrine and was significantly reduced in the presence of L-lactic acid. The transplacental pharmacokinetic model could adequately explain the transplacental transfer of diclofenac with influx clearances from maternal and fetal perfusates to placental tissue of 0.276 and 0.0345 ml/min/g cotyledon and efflux rate constants from placental tissue to maternal and fetal perfusates of 0.406 and 0.0337 min(-1), respectively. By taking into account protein binding, the placental tissue/plasma concentration ratio in humans for diclofenac was estimated to be 0.108 ml/g of cotyledon and was smaller than that of antipyrine. In conclusion, human placental perfusion and transplacental pharmacokinetic modeling allowed us to determine the transplacental transfer properties of diclofenac quantitatively. Diclofenac may share transplacental transfer system(s) with L-lactic acid.

Original languageEnglish
Pages (from-to)962-968
Number of pages7
JournalDrug metabolism and disposition: the biological fate of chemicals
Volume37
Issue number5
Publication statusPublished - 2009 May
Externally publishedYes

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Diclofenac
Placenta
Pharmacokinetics
Antipyrine
Lactic Acid
Cotyledon
Mothers
Protein Binding
Chlorides
Perfusion
Ions

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Shintaku, K., Hori, S., Tsujimoto, M., Nagata, H., Satoh, S., Tsukimori, K., ... Sawada, Y. (2009). Transplacental pharmacokinetics of diclofenac in perfused human placenta. Drug metabolism and disposition: the biological fate of chemicals, 37(5), 962-968.

Transplacental pharmacokinetics of diclofenac in perfused human placenta. / Shintaku, Kyohei; Hori, Satoko; Tsujimoto, Masayuki; Nagata, Hideaki; Satoh, Shoji; Tsukimori, Kiyomi; Nakano, Hitoo; Fujii, Tomoyuki; Taketani, Yuji; Ohtani, Hisakazu; Sawada, Yasufumi.

In: Drug metabolism and disposition: the biological fate of chemicals, Vol. 37, No. 5, 05.2009, p. 962-968.

Research output: Contribution to journalArticle

Shintaku, K, Hori, S, Tsujimoto, M, Nagata, H, Satoh, S, Tsukimori, K, Nakano, H, Fujii, T, Taketani, Y, Ohtani, H & Sawada, Y 2009, 'Transplacental pharmacokinetics of diclofenac in perfused human placenta.', Drug metabolism and disposition: the biological fate of chemicals, vol. 37, no. 5, pp. 962-968.
Shintaku K, Hori S, Tsujimoto M, Nagata H, Satoh S, Tsukimori K et al. Transplacental pharmacokinetics of diclofenac in perfused human placenta. Drug metabolism and disposition: the biological fate of chemicals. 2009 May;37(5):962-968.
Shintaku, Kyohei ; Hori, Satoko ; Tsujimoto, Masayuki ; Nagata, Hideaki ; Satoh, Shoji ; Tsukimori, Kiyomi ; Nakano, Hitoo ; Fujii, Tomoyuki ; Taketani, Yuji ; Ohtani, Hisakazu ; Sawada, Yasufumi. / Transplacental pharmacokinetics of diclofenac in perfused human placenta. In: Drug metabolism and disposition: the biological fate of chemicals. 2009 ; Vol. 37, No. 5. pp. 962-968.
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AU - Nakano, Hitoo

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