Application of 4-hydroxyantipyrine and acetaminophen O-sulfate as biodistribution promoter

Y. Ohkawa, Y. Kiyohara, T. Asoh, H. Maeda, M. Kurumi, Kenji Sasaki, Yuji Kurosaki, M. Matsumura, T. Nakayama

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The effects of 4-hydroxyantipyrine (4-OH), a major metabolite of antipyrine and its sulfate, 4-hydroxyantipyrine O-sulfate (4-S), on the pharmacokinetics of citicoline and thiopental sodium were investigated in rats. The concomitant use of 4-OH increased significantly the tissue-to-plasma concentration ratio (Kp) of citicoline in the brain and liver and that of thiopental sodium in the brain, liver, and heart, while 4-S did not affect them. The permeability clearance of blood-brain barrier (BBB) (Kin) and the total distribution volume (Vdbr) of citicoline were not affected by either 4-OH or 4-S. However, those of thiopental sodium were significantly increased by not only 4-OH but also by 4-S. On the other hand, the plasma concentration of antipyrine was significantly decreased by the intravenous bolus coadministration of N-acetyl-p-aminophenyl O-sulfate (APAPS) at steady-state plasma concentration of antipyrine. A similar reduction was not observed with the intravenous coadministration of acetaminophen (APAP). The Kp value of antipyrine was significantly increased in the brain by the coadministration of APAPS, but was not affected by APAP. The increment in the drug distribution to the brain with the concomitant use of 4-OH (or APAPS) observed in this study is useful information for the application of drug combinations as biodistribution promoters.

Original languageEnglish
Pages (from-to)1404-1410
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Volume24
Issue number12
DOIs
Publication statusPublished - 2001

Fingerprint

Antipyrine
Sulfates
Cytidine Diphosphate Choline
Thiopental
Acetaminophen
Brain
Liver
Drug Combinations
Blood-Brain Barrier
Permeability
Pharmacokinetics
acetaminophen sulfate ester
4-hydroxyantipyrine
Pharmaceutical Preparations

Keywords

  • 4-hydroxyantipyrine
  • Acetaminophen O-sulfate
  • Biodistribution promoter
  • Concomitant use

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Application of 4-hydroxyantipyrine and acetaminophen O-sulfate as biodistribution promoter. / Ohkawa, Y.; Kiyohara, Y.; Asoh, T.; Maeda, H.; Kurumi, M.; Sasaki, Kenji; Kurosaki, Yuji; Matsumura, M.; Nakayama, T.

In: Biological and Pharmaceutical Bulletin, Vol. 24, No. 12, 2001, p. 1404-1410.

Research output: Contribution to journalArticle

Ohkawa, Y, Kiyohara, Y, Asoh, T, Maeda, H, Kurumi, M, Sasaki, K, Kurosaki, Y, Matsumura, M & Nakayama, T 2001, 'Application of 4-hydroxyantipyrine and acetaminophen O-sulfate as biodistribution promoter', Biological and Pharmaceutical Bulletin, vol. 24, no. 12, pp. 1404-1410. https://doi.org/10.1248/bpb.24.1404
Ohkawa, Y. ; Kiyohara, Y. ; Asoh, T. ; Maeda, H. ; Kurumi, M. ; Sasaki, Kenji ; Kurosaki, Yuji ; Matsumura, M. ; Nakayama, T. / Application of 4-hydroxyantipyrine and acetaminophen O-sulfate as biodistribution promoter. In: Biological and Pharmaceutical Bulletin. 2001 ; Vol. 24, No. 12. pp. 1404-1410.
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