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

  • Tuomo NieminenEmail author
  • Hannu Uusitalo
  • Väinö Turjanmaa
  • Gunilla Bjärnhall
  • Hans Hedenström
  • Jukka Mäenpää
  • Auli Ropo
  • Pekka Heikkilä
  • Mika Kähönen
Pharmacodynamics

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.

Keywords

Pulse Wave Velocity Timolol Celiprolol Dorzolamide Stroke Index 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Tuomo Nieminen
    • 1
    Email author
  • Hannu Uusitalo
    • 4
  • Väinö Turjanmaa
    • 2
  • Gunilla Bjärnhall
    • 5
  • Hans Hedenström
    • 6
  • Jukka Mäenpää
    • 7
  • Auli Ropo
    • 8
  • Pekka Heikkilä
    • 9
  • Mika Kähönen
    • 2
    • 3
  1. 1.Department of Pharmacological Sciences, Medical SchoolUniversity of TampereTampereFinland
  2. 2.Department of Clinical Physiology, Medical SchoolUniversity of TampereTampereFinland
  3. 3.Tampere University HospitalTampereFinland
  4. 4.Department of OphthalmologyUniversity of Kuopio and Kuopio University HospitalFinland
  5. 5.Department of Neuroscience/OphthalmologyUniversity of UppsalaUppsalaSweden
  6. 6.Department of Clinical PhysiologyUniversity of UppsalaUppsalaSweden
  7. 7.Santen OyTampereFinland
  8. 8.Clinical ResearchSanten OyHelsinkiFinland
  9. 9.4Pharma LtdTurkuFinland

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