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Association between low plasma levels of ophthalmic timolol and haemodynamics in glaucoma patients

  • Pharmacodynamics
  • Published:
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Abstract

Objectives

The aims of the study were to assess the correlation between the plasma concentration of ophthalmic timolol and cardiovascular parameters, and the influence of timolol on advanced haemodynamic variables, such as stroke (SI), cardiac (CI) and systemic vascular resistance (SVRI) indices and arterial pulse wave velocity (PWV).

Methods

Twenty-five glaucoma or ocular hypertensive patients were treated with 0.5% aqueous and 0.1% hydrogel formulations of timolol using a randomised, double-masked, crossover, multicentre design. All the patients were subjected to passive head-up tilt, electrocardiography, exercise test and measurement of plasma concentration of timolol. In the analysis, the data on the two treatments were combined, and the Spearman correlation coefficients between the plasma level of timolol and physiological effects were calculated.

Results

During the head-up tilt test before rising the bed up, the resting heart rate (HR; R=−0.52, P=0.001) and PWV (R=−0.34, P=0.04) were inversely correlated with timolol level. In the upright position, ophthalmic timolol effectively suppressed the rise in HR (R=−0.36, P=0.03). The SI did not change with timolol concentration, while CI diminished as timolol concentration rose (R=−0.39, P=0.02). The SVRI correlated with timolol concentration (R=0.38, P=0.02). In the exercise test, correlation between HR and plasma level of timolol steadily grew stronger as the load increased, reaching R=−0.60 (P<0.0001) at the maximum load. Systolic and diastolic arterial pressures were not associated with the timolol concentration.

Conclusion

The plasma concentration of ophthalmic timolol correlates with several haemodynamic effects. As HR decreases, SVRI increases and blood pressure is kept unchanged.

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Acknowledgements

Study nurse Pirjo Järventausta is acknowledged for the skillful technical assistance. Financial support has been received from Medical Research Fund of Tampere University Hospital.

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Authors and Affiliations

  1. Department of Pharmacological Sciences, Medical School, University of Tampere, 33014, Tampere, Finland

    Tuomo Nieminen

  2. Department of Clinical Physiology, Medical School, University of Tampere, 33014, Tampere, Finland

    Väinö Turjanmaa & Mika Kähönen

  3. Tampere University Hospital, P.O. BOX 2000, 33521, Tampere, Finland

    Mika Kähönen

  4. Department of Ophthalmology, University of Kuopio and Kuopio University Hospital, Finland

    Hannu Uusitalo

  5. Department of Neuroscience/Ophthalmology, University of Uppsala, Uppsala, Sweden

    Gunilla Bjärnhall

  6. Department of Clinical Physiology, University of Uppsala, Uppsala, Sweden

    Hans Hedenström

  7. Santen Oy, Niittyhaankatu 20, 33, 33721, Tampere, Finland

    Jukka Mäenpää

  8. Clinical Research, Santen Oy, Helsinki, Finland

    Auli Ropo

  9. 4Pharma Ltd, Turku, Finland

    Pekka Heikkilä

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  1. Tuomo Nieminen
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  9. Mika Kähönen
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Correspondence to Tuomo Nieminen.

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Nieminen, T., Uusitalo, H., Turjanmaa, V. et al. Association between low plasma levels of ophthalmic timolol and haemodynamics in glaucoma patients. Eur J Clin Pharmacol 61, 369–374 (2005). https://doi.org/10.1007/s00228-005-0945-2

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  • DOI: https://doi.org/10.1007/s00228-005-0945-2

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