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European Journal of Clinical Pharmacology

, Volume 7, Issue 1, pp 25–29 | Cite as

Pharmacokinetics of unlabelled and14C-labelled pindolol in uraemia

  • E. E. Ohnhaus
  • E. Nüesch
  • J. Meier
  • F. Kalberer
Originals

Summary

The elimination of pindolol in 25 patients with various degrees of renal failure has been studied after an intravenous dose of 3 mg. A linear correlation was not found between the elimination rate of pindolol and the endogenous creatinine clearance, and the half-life of the unchanged drug was independent of the severity of the renal failure. This implies greater metabolism of pindolol in anuric patients and the extrarenal elimination rate constantkmwas increased. Three patients with severe renal failure were given 3 mg14C-pindolol. They showed almost constant plasma levels of radio-activity for 6 h and then slow excretion with a half-life of 48 h, because of accumulation of metabolites in the blood. Up to 90% of the metabolites are glucuronides and sulphates which have no beta-blocking or other clinical activity. Thus, to produce beta-adrenergic blockade the same dose of indolol is required in healthy patients as in those with uraemia.

Key words

Pindolol uraemia pharmacokinetics β-blockade 

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References

  1. 1.
    Bartels, H., Boehmer, M., Heierli, C.: Serum-Kreatinin-Bestimmung ohne Enteiweißen. Clin. chim. Acta37, 193–197 (1972)Google Scholar
  2. 2.
    Bricker, N.S., Morrin, P.A.F., Kime, S.W.: The pathologic physiology of chronic Bright's disease. Amer. J. Med.28, 77–98 (1960)Google Scholar
  3. 3.
    Dettli, L., Spring, P., Ryter, S.: Multiple dose kinetic and drug dosage in patients with kidney disease. Acta pharmacol. (Kbh.)29, Suppl. 3, 211–224 (1971)Google Scholar
  4. 4.
    Mannhart, M., Dettli, L., Spring, P.: Die Elimination des Doxizyklins und ihre Beeinflussung durch die Hämodialyse bei anurischen Patienten. Schweiz. Wschr.101, 123–127 (1971)Google Scholar
  5. 5.
    Pacha, W.L.: A method for the fluorimetric determination of 4-(2-hydroxy-3-isopropylaminopropoxy)-indole (LB 46), a β-blocking agent, in plasma and urine. Experientia (Basel)25, 802–803 (1969)Google Scholar
  6. 6.
    Schwarz, H.J.: The pharmacokinetics of LB 46 in man. Unpublished Sandoz Report 1970Google Scholar
  7. 7.
    Thompson, F.G., Joekes, A.M., Foulkes, P.M.: Pharmacodynamics of propranolol in renal failure. Brit. med. J.1972 II, 434–436Google Scholar
  8. 8.
    Traeger, A., Stein, G., Kunze, M., Zaumseil, J.: Zur Pharmakokinetik von Indomethazin bei nierengeschädigten Patienten. Int. J. clin. Pharmacol.6, 237–242 (1972)Google Scholar
  9. 9.
    Wagner, H.: Metabolismus von LB 46 beim Menschen und verschiedenen Tierspezies. Unpublished Sandoz Report 1970Google Scholar

Copyright information

© Springer-Verlag 1974

Authors and Affiliations

  • E. E. Ohnhaus
    • 1
    • 2
  • E. Nüesch
    • 1
  • J. Meier
    • 1
  • F. Kalberer
    • 1
  1. 1.Experimental Therapeutics Department, Biological and Medical Research Division and Biopharmaceutical SectionSandoz Ltd.BaselSwitzerland
  2. 2.Inselspital Med. UniversitätsklinikBernSwitzerland

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