Transdermal delivery of bupranolol: Pharmacodynamics and beta-adrenoceptor occupancy
- 32 Downloads
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 wordsbupranolol transdermal delivery system beta1- and beta2-adrenoceptor binding steady-state concentration healthy volunteers plasma concentrations beta-adrenoceptor antagonism
Unable to display preview. Download preview PDF.
- Chasseaud LF (1978) Pharmacokinetics and metabolism of bupranolol. In: Rahn KH, Schrey A (eds) Betablocker. Urban und Schwarzenberg, München Wien Baltimore, pp 30–33Google Scholar
- Kaumann AJ, Lemoine P (1985) Direct labelling of myocardial beta1-adrenoceptors. Comparison of binding affinity of3H-(--)-bisoprolol with it's blocking potency. Naunyn-Schmiedebergs Arch Pharmacol 331: 27–39Google Scholar
- Kenakin TP (1980) Effects of equilibration time on the attainment of equilibrium between antagonists and drug receptors. Eur J Pharmacol 66: 295–306Google Scholar
- Schild HO (1957) Drug antagonism and pAx. Pharmacol Rev 9: 242–246Google Scholar
- Vlasses PH, Ribeiro LGT, Rotmensch HH, Bondi JV, Loper AE, Hiches M, Dunlay MC, Ferguson RK (1985) Initial evaluation of transdermal timolol: Serum concentrations and beta-blockade. J Cardiovasc Pharmacol 7: 245–250Google Scholar
- Wellstein A, Palm D, Wiemer G, Schäfer-Korting M, Mutschler E (1984) Simple and reliable radioreceptor assay for beta-adrenoceptor antagonists and active metabolites in native human plasma. Eur J Clin Pharmacol 27: 545–553Google Scholar
- Wellstein A, Palm D, Pitschner HF, Belz GG (1985) Receptor binding of propranolol is the missing link between plasma concentration kinetics and the effect-time course in man. Eur J Clin Pharmacol 29: 131–147Google Scholar
- Wellstein A, Palm D, Belz GG (1986) Beta-adrenoceptor subtype mediated effects in man in comparison to in vitro beta1- and beta2-adrenoceptor occupancy. Naunyn-Schmiedeberg's Arch Pharmacol 332 [Suppl]: R 78Google Scholar
- Werning C (1978) Erfahrungen mit Bupranolol (Betadrenol) in der Hochdrucktherapie. In: Rahn KH, Schrey A (eds) Beta-blocker. Urban und Schwarzenberg, München Wien Baltimore, pp 123–125Google Scholar