Skip to main content
SpringerLink
Log in

The effect of paroxetine on the pharmacokinetics, safety, and tolerability of ramosetron in healthy subjects

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

Abstract

Objective

The aim of our study was to investigate the effects of multiple doses of paroxetine on the pharmacokinetics, safety, and tolerability of a single oral 10-µg dose of ramosetron.

Methods

This was an open, one-sequence crossover design study. On day 1, healthy male and female subjects were administered a single dose of 10 μg ramosetron. On the morning of day 3, the subjects were administered paroxetine to reach steady state, which consisted of morning doses of 20 mg on days 3–12. The dose on day 11 was administered in combination with a single dose of 10 μg ramosetron.

Results

In subjects genotyped as extensive CYP2D6 metabolizers, coadministration of paroxetine with ramosetron resulted in an increase in area under the curve from 0 to infinity (AUC0-inf) and the peak concentration (Cmax) of ramosetron by 1.14-fold (90% confidence interval (CI): 1.07–1.22) and by 1.06-fold (90% CI: 1.00–1.11), respectively.

Conclusions

It can be concluded that the single-dose pharmacokinetic profile of ramosetron 10 μg is not affected to a clinically relevant degree by paroxetine 20 mg once daily administered for 10 days.

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

Similar content being viewed by others

References

  1. Gralnek IM, Hays RD, Kilbourne A, Naliboff B, Mayer EA (2002) The impact of irritable bowel syndrome on health-related quality of life. Gastroenterol 119:654–660

    Article  Google Scholar 

  2. Gershon MD (1999) Review article: roles played by 5-hydroxytryptamine in the physiology of the bowel. Aliment Pharmacol Ther 13(Suppl 2):15–30

    PubMed  Google Scholar 

  3. Delvaux M, Louvel D, Mamet JP, Campos-Oriola R, Frexinos J (1998) Effect of alosetron on responses to colonic distension in patients with irritable bowel syndrome. Aliment Pharmacol Ther 12:849–855

    Article  PubMed  CAS  Google Scholar 

  4. Forster JM, Houghton LA, Whorwell PJ (1997) Alosetron shows colonic transit in patients with irritable bowel syndrome (IBS). Gastroenterol 112:A732. (Abstract)

    Google Scholar 

  5. Northcutt AR, Camilleri M, Mayer EA et al (1998) Alosetron, a 5HT3-receptor antagonist, is effective in the treatment of female irritable bowel syndrome patients. Gastroenterol 114:A812. (Abstract)

    Article  Google Scholar 

  6. Nakashima M, Kanemaru, M, Miura, H, Takeshige, T, Atsuta, Y (1995) Phase I clinical study of oral ramosetron. Rinsyo to Kenkyu 72(11):264–278

    Google Scholar 

  7. Astellas Pharma Inc., Investigator’s Brochure (2005) YM060 Ramosetron Hydrochloride

  8. Castle MZD, Silk DBA, Libby GW (2004) Review article: the rationale for antidepressant therapy in functional gastrointestinal disorders. Aliment Pharmacol Ther 19:969–979

    Article  PubMed  CAS  Google Scholar 

  9. Clouse RE, Lustman PJ (2005) Use of psychopharmacological agents for functional gastrointestinal disorders. Gut 54:1332–1341

    Article  PubMed  CAS  Google Scholar 

  10. American Gastroenterological Association Medical Position Statement: Irritable Bowel Syndrome (2002) Gastroenterol 123:2105–2107

    Article  Google Scholar 

  11. Creed F, Fernandes L, Guthrie E et al (2003) The cost effectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome. Gastroenterol 124:303–317

    Article  Google Scholar 

  12. Lea R, Whorwell PJ (2003) New insights into the psychosocial aspects of irritable bowel syndrome. Curr Gastroenterol Rep 5:343–350

    Article  PubMed  Google Scholar 

  13. Crewe HK, Lennard MS, Tucker GT, Woods FR, Haddock RE (1992) The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes. Br J Clin Pharmacol 34:262–265

    PubMed  CAS  Google Scholar 

  14. Schwartz JB (2003) The influence of sex on pharmacokinetics. Clin Pharmacokinet 42:107–121

    Article  PubMed  CAS  Google Scholar 

  15. Koch KM, Palmer JL, Noordin N, Tomlinson JJ, Baidoo, C (2002) Sex and age differences in the pharmacokinetics of alosetron. Br J Clin Pharmacol 53:238–242

    Article  PubMed  CAS  Google Scholar 

  16. Pritchard JF, Bryson JC, Kernodle AE, Benedetti TL, Powell JR (1992) Age and gender effects on ondansetron pharmacokinetics: evaluation of healthy aged volunteers. Clin Pharmacol Ther 51:51–55

    PubMed  CAS  Google Scholar 

  17. Koch KM, Corrigan BW, Manzo J et al (2004) Alosetron repeat dose pharmacokinetics, effects on enzyme activities, and influence of demographic factors. Aliment Pharmacol Ther 20:223–230

    Article  PubMed  CAS  Google Scholar 

  18. Dixon CM, Colthup PV, Serabjit-Singh CJ et al (1995) Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. Drug Metab Dispos 23:1225–1230

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Pharmacology, Astellas Pharma Inc., 3-17-1, Hasune, Itabashi-ku, Tokyo, 174-8612, Japan

    Takeshi Kadokura

  2. Exploratory Development, Astellas Pharma Europe B. V., Elisabethhof 19, P.O. Box 108, 2350, AC, Leiderdorp, The Netherlands

    Martin den Adel & Walter J. J. Krauwinkel

  3. Drug Metabolism Research Laboratories, Astellas Pharma Inc., 2-1-6, Kashima, Yodogawa-ku, Osaka, 532-8514, Japan

    Tetsuo Takeshige

  4. Project Management, Astellas Pharma Inc., 3-17-1, Hasune, Itabashi-ku, Tokyo, 174-8612, Japan

    Akito Nishida

Authors
  1. Takeshi Kadokura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martin den Adel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Walter J. J. Krauwinkel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tetsuo Takeshige
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akito Nishida
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takeshi Kadokura.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kadokura, T., den Adel, M., Krauwinkel, W.J.J. et al. The effect of paroxetine on the pharmacokinetics, safety, and tolerability of ramosetron in healthy subjects. Eur J Clin Pharmacol 64, 605–609 (2008). https://doi.org/10.1007/s00228-008-0472-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-008-0472-z

Keywords

Search

Navigation