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Propranolol in conscious spontaneously hypertensive rats

II. Disposition after subcutaneous and intracerebroventricular administration

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Summary

The disposition of dl-propranolol was studied in spontaneously hypertensive rats (SHR), both after subcutaneous (s.c.) and intracerebroventricular (i.c.v.) injection of 1 mg/kg.

  1. 1.

    Upon s.c. injection propranolol appeared rapidly in plasma. A maximum concentration of 374 ± 33 ng/ml (N=10) was reached 5 min after injection. After a distribution phase with a half-life of t 1/2α=17 min propranolol was eliminated with a t 1/2β=59 min.

  2. 2.

    Both propranolol and its metabolites were taken up rapidly into all tissues studied. Highest concentrations (10.4±1.5 μg/g, N=5) were found in lungs 30 min after injection.

  3. 3.

    Neither propranolol nor its metabolites accumulated in any of the tissues examined.

  4. 4.

    Upon i.c.v. injection of propranolol, a maximal concentration of 573±47 ng/ml (N=3) was reached in plasma already 2 min after injection. In this case t 1/2α was 13 min and t 1/2β was 80 min.

  5. 5.

    Dialysis experiments indicated that propranolol is bound to plasma proteins for 92% in the concentration range of 20–100 ng/ml. With increasing concentrations binding diminishes progressively. At the highest concentration tested (345 ng/ml) only 76% was bound.

It is concluded that s.c. and i.c.v. injection of an identical dose of propranolol gives a similar plasma concentration-time profile. Moreover, it is suggested that the pharmacokinetic behaviour of propranolol in SHR does not explain the delayed antihypertensive effect of this drug.

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Authors and Affiliations

  1. Department of Pharmacology, Rijksuniversiteit Limburg, Postbus 616, NL-6200 MD, Maastricht, The Netherlands

    J. F. M. Smits & H. A. J. Struyker-Boudier

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  1. J. F. M. Smits
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  2. H. A. J. Struyker-Boudier
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Smits, J.F.M., Struyker-Boudier, H.A.J. Propranolol in conscious spontaneously hypertensive rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 309, 19–24 (1979). https://doi.org/10.1007/BF00498752

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