Skip to main content
Log in

Elimination of flecainide as a function of urinary flow rate and pH

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

Summary

In order to evaluate the influence of urinary flow rate at different pH values on the pharmacokinetics of the basic antiarrhythmic drug flecainide 7 healthy men received 50 mg flecainide under 4 different conditions:

  1. 1.

    acidic urine (pH 5) and a high fluid load (125 ml · h−1)

  2. 2.

    acidic urine (pH 5) and a low fluid load (25 ml · h−1)

  3. 3.

    alkaline urine (pH 8) and a high fluid load (125 ml · h−1)

  4. 4.

    alkaline urine (pH 8) and a low fluid load (25 ml · h−1)

At acidic pH the half-life, the amount of unchanged drug in the urine (Ae), renal clearance (CLR) and area under the curve (AUC) were independent of the fluid load.

At alkaline pH Ae (5.8 vs 2.6 mg) and CLR (73 vs 33 ml · min−1) were significantly affected by fluid load (high vs low), whereas half-life and AUC were not different (15.7 vs 16.0 h, 1480 vs 1540 ng · ml−1 · h). When comparing acidic and alkaline urinary pH conditions, half-life, Ae, CLR, and AUC were different. For a high fluid load the values at acidic vs alkaline pH were half-life 10.0 vs 15.7 h; Ae 15.9 vs 5.8 mg; CLR 288 vs 73 ml · min−1; AUC 976 vs 1480 ng · ml−1 · h. For a low fluid load the corresponding values at acidic vs alkaline pH were half-life 10.1 vs 16.0 h; Ae 15.9 vs 2.6 mg; CLR 267 vs 33 ml · min−1; AUC 1045 vs 1540 ng · ml−1 · h.

It is concluded that urinary pH affects flecainide pharmacokinetics independently of urinary flow rate, and that a high flow enhances the elimination of flecainide only with an alkaline urine. This effect of flow rate does not appear to be of clinical relevance.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Chang SF, Miller AM, Fox JM, Welscher TM (1984) Application of a bonded-phase extraction column for rapid sample preparation of flecainide from human plasma for HPLC analysis-detection by fluorescence or U.V. Ther Drug Monit 6: 105–111

    Google Scholar 

  • Harrison DC, Winkle RA, Sami M, Mason JW (1981) Encainide: a new and potent antiarrhythmic agent. In: Harrison DC (ed) Cardiac arrhythmias, a decade of progress. GK Hall Medical Publishers, Boston

    Google Scholar 

  • Holmes B, Heel RC (1985) Flecainide, a preliminary review of its pharmacodynamic properties and therapeutic efficacy. Drugs 29: 1–33

    Google Scholar 

  • Holm ST (1979) A simple sequentially rejective multiple test procedure Scand J Stat 6: 65–70

    Google Scholar 

  • Johnston A, Warrington S, Turner P (1985) Flecainide pharmacokinetics in healthy volunteers: the influence of urinary pH. Br J Clin Pharmacol 20: 333–338

    Google Scholar 

  • Muhiddin KA, Johnston A, Turner P (1984) The influence of urinary pH on flecainide excretion and its serum pharmacokinetics. Br J Clin Pharmacol 17: 447–451

    Google Scholar 

  • Sachs L (1978) Angewandte Statistik. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Salerno DM, Ganrud G, Sharkey P, Krejci J, Larson T, Erlien D, Berry D, Hodges M (1986) Pharmacodynamics and side effects of flecainide acetate. Clin Pharmacol Ther 40: 101–107

    Google Scholar 

  • Vaughan Williams EM (1970) Classification of antiarrhythmic drugs. In: Sandoe E, Flensted-Jansen E, Olesen KH (eds) Symposium on cardiac arrhythmias. AB Astra Sodertalje, Sweden, pp 449–472

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Dedicated to Prof. Ernst Mutschler on the occasion of his 60th birthday

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hertrampf, R., Gundert-Remy, U., Beckmann, J. et al. Elimination of flecainide as a function of urinary flow rate and pH. Eur J Clin Pharmacol 41, 61–63 (1991). https://doi.org/10.1007/BF00280108

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00280108

Key words

Navigation