Skip to main content
SpringerLink
Log in

Effects of dosing interval on the pharmacokinetic and pharmacodynamic interactions between the oral adsorbent AST-120 and triazolam in humans

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

The objective of this study was to evaluate the pharmacokinetic and pharmacodynamic interactions between the oral adsorbent AST-120 and triazolam.

Methods

In this randomized, cross-over study, 12 healthy volunteers received a single oral dose of triazolam 0.25 mg alone or with AST-120 2 g given 0, 30 or 60 min before triazolam administration.

Results

The area under the plasma triazolam concentration–time curve (AUC0-∞) significantly decreased with simultaneous AST-120 + triazolam (alone vs simultaneous: 10.9 ± 6.0 vs 6.4 ± 2.6 ng·h/mL, p = 0.003). Triazolam-induced impairment in psychomotor performance assessed by the digit symbol substitution test was significantly attenuated when AST-120 was administered simultaneously. No significant changes in pharmacokinetic and pharmacodynamic parameters were observed when AST-120 was given 30 or 60 min before triazolam administration.

Conclusions

Administering AST-120 simultaneously with triazolam affects the pharmacokinetics and pharmacodynamics of triazolam. Dosing AST-120 at least 30 min before triazolam administration may avoid these interactions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Miyazaki Y, Yakou S, Asayama T, Kouno H, Sakurai S, Yanagawa C (2008) Comparison of physicochemical and adsorptive properties of brand-name and generic spherical carbon adsorbents. Jpn J Pharm Health Care Sci 34:1077–1085

    Article  CAS  Google Scholar 

  2. Tanizawa K, Ohashi H (1998) Influence of KREMEZIN™ on serum concentration in aspirin administration. Jpn J Hosp Pharm 24:383–388

    Article  CAS  Google Scholar 

  3. Tanaka C, Ohtani H, Tsujimoto M et al (2007) Effects of dosing interval on the pharmacokinetic interaction between oral small spherical activated charcoal and amlodipine in humans. J Clin Pharmacol 47:904–908

    Article  PubMed  CAS  Google Scholar 

  4. Marier JF, Guilbaud R, Kambhampati SR et al (2006) The effect of AST-120 on the single-dose pharmacokinetics of losartan and losartan acid (e-3174) in healthy subjects. J Clin Pharmacol 46:310–320

    Article  PubMed  CAS  Google Scholar 

  5. Gusbeth-Tatomir P, Boisteanu D, Seica A, Buga C, Covic A (2007) Sleep disorders: a systematic review of an emerging major clinical issue in renal patients. Int Urol Nephrol 39:1217–1226

    Article  PubMed  Google Scholar 

  6. Sugimoto K, Araki N, Ohmori M et al (2006) Interaction between grapefruit juice and hypnotic drugs: comparison of triazolam and quazepam. Eur J Clin Pharmacol 62:209–215

    Article  PubMed  CAS  Google Scholar 

  7. Misaka S, Uchida S, Imai H et al (2010) Pharmacokinetics and pharmacodynamics of low doses of midazolam administered intravenously and orally to healthy volunteers. Clin Exp Pharmacol Physiol 37:290–295

    Article  PubMed  CAS  Google Scholar 

  8. Liang KY, Zeger SL (1986) Longitudinal Data analysis using generalized linear models. Biometrika 73:13–22

    Article  Google Scholar 

  9. Levy G (1982) Gastrointestinal clearance of drugs with activated charcoal. N Engl J Med 307:676–678

    Article  PubMed  CAS  Google Scholar 

  10. Berlinger WG, Spector R, Goldberg MJ, Johnson GF, Quee CK, Berg MJ (1983) Enhancement of theophylline clearance by oral activated charcoal. Clin Pharmacol Ther 33:351–354

    Article  PubMed  CAS  Google Scholar 

  11. Lalonde RL, Deshpande R, Hamilton PP, McLean WM, Greenway DC (1985) Acceleration of digoxin clearance by activated charcoal. Clin Pharmacol Ther 37:367–371

    Article  PubMed  CAS  Google Scholar 

  12. Berg MJ, Berlinger WG, Goldberg MJ, Spector R, Johnson GF (1982) Acceleration of the body clearance of phenobarbital by oral activated charcoal. N Engl J Med 307:642–644

    Article  PubMed  CAS  Google Scholar 

  13. Gibbons RD, Brown BWM, Azarnoff DL et al (1999) Assessment of the Safety and Efficacy Data for the Hypnotic Halcion®: Results of an Analysis by an Institute of Medicine Committee. J Am Stat Assoc 94:993–1002

    Google Scholar 

Download references

Acknowledgements

The authors are grateful to Ms. Michiyo Kageyama for her excellent technical assistance.

Conflict of interest

Kyoichi Ohashi has received research funding from Kureha Corporation, Tokyo, Japan. The other authors declared no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology and Therapeutics, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan

    Tsutomu Kotegawa, Hajime Morita, Hiromistu Imai, Misaki Morita, Tsuneaki Yoshizato & Kyoichi Ohashi

  2. Department of Pharmaceutical Medicine and Communication, Oita University Faculty of Medicine, Oita, Japan

    Kimiko Tsutsumi

  3. Department of Statistics, Oita University Faculty of Medicine, Oita, Japan

    Tetsuji Ohyama

  4. Department of Pharmacy Practice and Science, University of Shizuoka School of Pharmaceutical Sciences, Shizuoka, Japan

    Shinya Uchida & Noriyuki Namiki

  5. Department of Clinical Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Hiroshi Watanabe

Authors
  1. Tsutomu Kotegawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kimiko Tsutsumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hajime Morita
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiromistu Imai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Misaki Morita
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tsuneaki Yoshizato
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tetsuji Ohyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shinya Uchida
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hiroshi Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Noriyuki Namiki
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kyoichi Ohashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tsutomu Kotegawa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kotegawa, T., Tsutsumi, K., Morita, H. et al. Effects of dosing interval on the pharmacokinetic and pharmacodynamic interactions between the oral adsorbent AST-120 and triazolam in humans. Eur J Clin Pharmacol 68, 1605–1610 (2012). https://doi.org/10.1007/s00228-012-1301-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-012-1301-y

Keywords

Search

Navigation