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Oral absorption of propiverine solution and of the immediate and extended release dosage forms: influence of regioselective intestinal elimination

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

Abstract

Purpose

The muscarine receptor antagonist propiverine in immediate release tablet form (IR) undergoes presystemic elimination mediated by CYP450 enzymes and intestinal efflux transporters. The aim of our study with propiverine IR and extended release (ER) was to determine whether propiverine disposition is dose linear, to compare the pharmacokinetics of propiverine in oral solution with IR and ER and to show how absorption rate is associated with bioavailability.

Methods

The pharmacokinetics of propiverine administered as intravenous propiverine (15 mg), 10, 15, and 30 mg propiverine IR, an oral propiverine solution (15 mg) and 10, 15, 30, and 45 mg propiverine ER were measured in two randomized, controlled, single-dose, five-period, cross-over studies, with each case involving a study cohort of ten healthy Caucasian subjects.

Results

Disposition of propiverine IR and ER was not dose-related. The bioavailability of ER was 64.5 ± 16.1% compared to 50.3 ± 13.4% (non-significant) after administration of the IR and propiverine solution (42.6 ± 14.8%, p < 0.05). The mean absorption time (MAT) of ER (14.2 ± 4.79 h) was significantly longer than that of the solution and IR (3.94 ± 4.14 and 0.38 ± 3.79 h, respectively; both p < 0.05). The bioavailability of propiverine was significantly correlated to the MAT (r = 0.521, p < 0.001). Renal excretion of the metabolite M-23 after propiverine ER administration (6.7 ± 2.7%) was significantly lower than that after administration of the oral solution (10 ± 2.2%) and of IR (9.8 ± 2.7%; both p < 0.05).

Conclusions

The bioavailability of propiverine appears to be dependent on the intestinal site of dissolution and, consequently, on the extent of presystemic intestinal elimination.

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Abbreviations

ABCB1:

P-glycoprotein

ABCC2:

Multidrug resistance-associated protein 2 (MRP2)

Propiverine IR:

propiverine in immediate release dosage form

Propiverine ER:

propiverine in extended release dosage form

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Acknowledgements

The authors are indebted to Hannelore Kreher and Renate Peters for their excellent technical assistance. This work was supported by an institutional grant of APOGEPHA Arzneimittel GmbH Dresden and the German Federal Ministry for Education and Research (grant 01 GG 9845/5, 01 ZZ 0103). Manfred Braeter is an employee of APOGEPHA. All other authors have no conflict of interest.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, Ernst Moritz Arndt University, Friedrich-Loeffler-Str. 23d, 17487, Greifswald, Germany

    Karen May, Thomas Giessmann, Danilo Wegner, Christiane Modess, Stefan Oswald & Werner Siegmund

  2. Institute of Clinical Pharmacology, University of Technology, Dresden, Germany

    Reinhard Oertel

  3. APOGEPHA Arzneimittel GmbH, Dresden, Germany

    Manfred Braeter

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  1. Karen May
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  2. Thomas Giessmann
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Correspondence to Werner Siegmund.

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May, K., Giessmann, T., Wegner, D. et al. Oral absorption of propiverine solution and of the immediate and extended release dosage forms: influence of regioselective intestinal elimination. Eur J Clin Pharmacol 64, 1085–1092 (2008). https://doi.org/10.1007/s00228-008-0528-0

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  • DOI: https://doi.org/10.1007/s00228-008-0528-0

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