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European Journal of Clinical Pharmacology

, Volume 10, Issue 5, pp 319–324 | Cite as

Investigation of the pharmacodynamics and pharmacokinetics of 2-(2,4-Dimethoxyphenyl)-Imidazo-[4,5-b]-pyridine hydrochloride (AR-L 57 CL) in man

  • G. G. Belz
  • H. Nübling
  • A. Zimmer
Originals

Summary

AR-L 57 CL is an imidazole derivative which has been shown in animal studies to have a pronounced positive inotropic effect. This effect and the pharmacokinetics of AR-L 57 CL have been investigated by non-invasive methods in 8 healthy volunteers. After a single intravenous dose of 200 mg, administered as part of Phase 1 of the clinical studies, AR-L 57 CL plasma concentrations were measured by fluorimetry at intervals for up to one hour. Its inotropic action on the heart was demonstrated by changes in the systolic time intervals: QS2 = duration of electro-mechanical systole; PEP = pre-ejection period; LVET = left ventricular ejection time. The decrease in plasma concentration could be expressed in terms of an open two-compartment pharmacokinetic model. The shorter elimination phase had a t1/2 of 4 min and the longer a t1/2 of 30 min. Immediately after injection, QS2 and PEP (corrected for heart rate) as well as PEP/LVET (independent of heart rate) decreased considerably. They had returned to normal by 22 min after injection. The plasma concentrations of AR-L 57 CL of 2 – 5 µg-equivalents/ml showed a highly significant correlation with the decrease in systolic time intervals. Both systolic and diastolic blood pressure rose briefly after injection. The AV conduction time fell initially and the heart-rate increased briefly. Thus AR-L 57 CL was shown to be a short acting drug with a high degree of positive inotropic action. It did not cause bradycardia or increase atrioventricular transmission time and appeared to be easily controllable.

Key words

Positively inotropic drug imidazole derivative i.v.-injection pharmacodynamic effects systolic time intervals plasma levels 

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Copyright information

© Springer-Verlag 1976

Authors and Affiliations

  • G. G. Belz
    • 1
    • 2
    • 3
    • 4
  • H. Nübling
    • 1
    • 2
    • 3
  • A. Zimmer
    • 1
    • 2
    • 3
  1. 1.Department of PharmacologyUniversity of UlmGermany
  2. 2.Cardiology and Angiology SectionUniversity of UlmGermany
  3. 3.Department of BiochemistryDr. Karl Thomae GmbHBiberach/RissGermany
  4. 4.Bundeswehrzentralkrankenhaus KoblenzKoblenzGermany

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