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Pharmacokinetic Evaluation of (Glycolato‐O, O′) diammine Platinum(II) in Lung Lymph in Sheep

The pharmacokinetics of (glycolato‐O, O′)diammine platinum(II) (254‐S), especially the distribution and behavior in the lung lymph in sheep, was investigated and compared with that of cis‐diammine‐dichloroplatinum(II) (CDDP). The blood and lung lymph fluid were collected from the carotid artery and...

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Autores principales: Koizumi, Tomonobu, Kubo, Keishi, Shinozaki, Shirou, Koyama, Shigeru, Amari, Toshiya, Hayano, Toshihide, Fujimoto, Keisaku, Kobayashi, Toshio, Sekiguchi, Morie, Sakai, Ryosuke, Ohshima, Taeyuki, Miyamoto, Ken‐ichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 1993
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919307/
https://www.ncbi.nlm.nih.gov/pubmed/8514614
http://dx.doi.org/10.1111/j.1349-7006.1993.tb00160.x
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author Koizumi, Tomonobu
Kubo, Keishi
Shinozaki, Shirou
Koyama, Shigeru
Amari, Toshiya
Hayano, Toshihide
Fujimoto, Keisaku
Kobayashi, Toshio
Sekiguchi, Morie
Sakai, Ryosuke
Ohshima, Taeyuki
Miyamoto, Ken‐ichi
author_facet Koizumi, Tomonobu
Kubo, Keishi
Shinozaki, Shirou
Koyama, Shigeru
Amari, Toshiya
Hayano, Toshihide
Fujimoto, Keisaku
Kobayashi, Toshio
Sekiguchi, Morie
Sakai, Ryosuke
Ohshima, Taeyuki
Miyamoto, Ken‐ichi
author_sort Koizumi, Tomonobu
collection PubMed
description The pharmacokinetics of (glycolato‐O, O′)diammine platinum(II) (254‐S), especially the distribution and behavior in the lung lymph in sheep, was investigated and compared with that of cis‐diammine‐dichloroplatinum(II) (CDDP). The blood and lung lymph fluid were collected from the carotid artery and a lung lymph fistula, respectively, in conscious sheep following intravenous infusion of 100 mg/body of 254‐S and CDDP for 30 min. The concentrations of these platinum complexes were measured by using atomic absorption spectrometry. We analyzed the data using an anatomically based model including part of the lymphatic circulation. The ultrafilterable platinum of 254‐S showed much larger area under the curve (AUC) and transfer rate constants than that of CDDP, even though the mean residence times were the same. The total platinum showed the opposite pharmacokinetic behavior. In anesthetized sheep, when lung tissue samples were obtained by biopsy at the same times as those of blood and lung lymph sampling after infusion of these drugs, 254‐S distributed in lung tissue appeared to move more easily into lung lymph than CDDP, which tended to be retained in lung tissue. These differences in pharmacokinetic behavior between 254‐S and CDDP seemed to be caused by differences in their strength of protein binding, the association constants of 254‐S for plasma and lymph protein were much less than those of CDDP. From these results, 254‐S may have favorable therapeutic effects on intrathoracic malignacies such as lung cancer and lymph metastasis
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spelling pubmed-59193072018-05-11 Pharmacokinetic Evaluation of (Glycolato‐O, O′) diammine Platinum(II) in Lung Lymph in Sheep Koizumi, Tomonobu Kubo, Keishi Shinozaki, Shirou Koyama, Shigeru Amari, Toshiya Hayano, Toshihide Fujimoto, Keisaku Kobayashi, Toshio Sekiguchi, Morie Sakai, Ryosuke Ohshima, Taeyuki Miyamoto, Ken‐ichi Jpn J Cancer Res Article The pharmacokinetics of (glycolato‐O, O′)diammine platinum(II) (254‐S), especially the distribution and behavior in the lung lymph in sheep, was investigated and compared with that of cis‐diammine‐dichloroplatinum(II) (CDDP). The blood and lung lymph fluid were collected from the carotid artery and a lung lymph fistula, respectively, in conscious sheep following intravenous infusion of 100 mg/body of 254‐S and CDDP for 30 min. The concentrations of these platinum complexes were measured by using atomic absorption spectrometry. We analyzed the data using an anatomically based model including part of the lymphatic circulation. The ultrafilterable platinum of 254‐S showed much larger area under the curve (AUC) and transfer rate constants than that of CDDP, even though the mean residence times were the same. The total platinum showed the opposite pharmacokinetic behavior. In anesthetized sheep, when lung tissue samples were obtained by biopsy at the same times as those of blood and lung lymph sampling after infusion of these drugs, 254‐S distributed in lung tissue appeared to move more easily into lung lymph than CDDP, which tended to be retained in lung tissue. These differences in pharmacokinetic behavior between 254‐S and CDDP seemed to be caused by differences in their strength of protein binding, the association constants of 254‐S for plasma and lymph protein were much less than those of CDDP. From these results, 254‐S may have favorable therapeutic effects on intrathoracic malignacies such as lung cancer and lymph metastasis Blackwell Publishing Ltd 1993-04 /pmc/articles/PMC5919307/ /pubmed/8514614 http://dx.doi.org/10.1111/j.1349-7006.1993.tb00160.x Text en
spellingShingle Article
Koizumi, Tomonobu
Kubo, Keishi
Shinozaki, Shirou
Koyama, Shigeru
Amari, Toshiya
Hayano, Toshihide
Fujimoto, Keisaku
Kobayashi, Toshio
Sekiguchi, Morie
Sakai, Ryosuke
Ohshima, Taeyuki
Miyamoto, Ken‐ichi
Pharmacokinetic Evaluation of (Glycolato‐O, O′) diammine Platinum(II) in Lung Lymph in Sheep
title Pharmacokinetic Evaluation of (Glycolato‐O, O′) diammine Platinum(II) in Lung Lymph in Sheep
title_full Pharmacokinetic Evaluation of (Glycolato‐O, O′) diammine Platinum(II) in Lung Lymph in Sheep
title_fullStr Pharmacokinetic Evaluation of (Glycolato‐O, O′) diammine Platinum(II) in Lung Lymph in Sheep
title_full_unstemmed Pharmacokinetic Evaluation of (Glycolato‐O, O′) diammine Platinum(II) in Lung Lymph in Sheep
title_short Pharmacokinetic Evaluation of (Glycolato‐O, O′) diammine Platinum(II) in Lung Lymph in Sheep
title_sort pharmacokinetic evaluation of (glycolato‐o, o′) diammine platinum(ii) in lung lymph in sheep
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919307/
https://www.ncbi.nlm.nih.gov/pubmed/8514614
http://dx.doi.org/10.1111/j.1349-7006.1993.tb00160.x
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