Association between low plasma levels of ophthalmic timolol and haemodynamics in glaucoma patients
- 196 Downloads
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).
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.
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.
The plasma concentration of ophthalmic timolol correlates with several haemodynamic effects. As HR decreases, SVRI increases and blood pressure is kept unchanged.
KeywordsPulse Wave Velocity Timolol Celiprolol Dorzolamide Stroke Index
Study nurse Pirjo Järventausta is acknowledged for the skillful technical assistance. Financial support has been received from Medical Research Fund of Tampere University Hospital.
- 7.Umetsuki MH, Kotegawa T, Nakamura K, Nakano S, Nakatsuka K (1997) Temporal variation in the effects of ophthalmic timolol on cardiovascular and respiratory functions in healthy men. J Clin Pharmacol 37:58–63Google Scholar
- 8.Stewart WC, Stewart JA, Crockett S, Kubilus C, Brown A, Shams N (2002) Comparison of the cardiovascular effects of unoprostone 0.15%, timolol 0.5% and placebo in healthy adults during exercise using a treadmill test. Acta Ophthalmol Scand 80:272–276Google Scholar
- 11.Takahashi N, Iwasaka T, Sugiura T, Onoyama H, Kurihara S, Inada M, Miki H, Uyama M (1989) Effect of coenzyme Q10 on hemodynamic response to ocular timolol. J Cardiovasc Pharmacol 14:462–468Google Scholar
- 20.Vuori ML, Ali-Melkkila T, Kaila T, Iisalo E, Saari KM (1993) Plasma and aqueous humour concentrations and systemic effects of topical betaxolol and timolol in man. Acta Ophthalmol (Copenh) 71:201–206Google Scholar
- 25.Kähönen M, Ylitalo R, Kööbi T, Turjanmaa V, Ylitalo P (2002) Influences of nonselective, β1-selective and vasodilatory β1-selective beta-blockers on arterial pulse wave velocity in normotensive subjects. Gen Pharmacol 35:219–224Google Scholar