European Journal of Clinical Pharmacology

, Volume 31, Issue 4, pp 419–422 | Cite as

Transdermal delivery of bupranolol: Pharmacodynamics and beta-adrenoceptor occupancy

  • A. Wellstein
  • H. Küppers
  • H. F. Pitschner
  • D. Palm
Originals

Summary

Bupranolol is a non-selective beta-adrenoceptor antagonist with a Ki-value of 6–15 nmol/l (equivalent to 1.5–4 ng/ml in plasma) at beta1- (rat salivary gland) and beta2-adrenoceptors (rat reticulocytes) in receptor binding studies with3H-CGP 12177 in the presence of human plasma. After oral administration of 200 mg bupranolol to healthy volunteers, the maximal plasma concentration was observed within 1.2 h but it only reached a level close to the Ki-value. Elimination from plasma was rapid (t1/2=2.0 h).

Administration of 30 mg bupranolol in a transdermal delivery system (TTS) every 24 h to 6 healthy volunteers for 72 h yielded steady state plasma concentrations 4- to 5-times above the Ki-value as shown by in vitro inhibition of beta-adrenoceptor binding by plasma samples. The pharmacodynamic effect, measured as the reduction in exercise tachycardia, showed a stable inhibitory effect; antagonism of a bolus injection of isoprenaline indicated a 10- to 15-fold right shift of the dose-response curve during the observation period of 72 h.

It is concluded that steady-state plasma concentrations and effect of the elsewise rapidly eliminated beta-blocker bupranolol can be achieved by a transdermal delivery system applied each day.

Key words

bupranolol transdermal delivery system beta1- and beta2-adrenoceptor binding steady-state concentration healthy volunteers plasma concentrations beta-adrenoceptor antagonism 

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Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • A. Wellstein
    • 1
  • H. Küppers
    • 2
  • H. F. Pitschner
    • 1
  • D. Palm
    • 1
  1. 1.Zentrum der PharmakologieKlinikum der J. W. Goethe-UniversitätFrankfurtGermany
  2. 2.Schwarz GmbHMonheimGermany

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