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Published on: March 12, 2016
Ophthalmic timolol: plasma concentration and systemic cardiopulmonary effects
T Nieminen1, T Lehtimäki, J Mäenpää
1Department of Pharmacological Sciences, Medical School, University of Tampere, Finland. tuomo.nieminen@iki.fi
Summary
Ophthalmic timolol, used for glaucoma, can cause systemic beta-blockade. Gel formulations reduce this risk, but individuals with poor CYP2D6 enzyme activity may still experience bradycardia.
Area of Science:
- Pharmacology
- Ophthalmology
- Clinical Pharmacy
Background:
- Timolol maleate is a non-selective beta-blocker used topically for glaucoma.
- Ophthalmic timolol can be absorbed systemically, causing beta-adrenergic blockade.
- Gel formulations aim to minimize systemic absorption compared to aqueous solutions.
Purpose of the Study:
- To evaluate the systemic effects of ophthalmic timolol formulations.
- To compare systemic absorption and effects of aqueous versus hydrogel formulations.
- To investigate the role of cytochrome P450 2D6 (CYP2D6) in timolol pharmacokinetics and pharmacodynamics.
Main Methods:
- Comparison of 0.5% aqueous and 0.1% hydrogel timolol formulations.
- Measurement of heart rate (HR), systolic (SAP) and diastolic (DAP) arterial pressures, and pulmonary parameters (PEF, FEV1).
- Analysis of plasma timolol levels and correlation with CYP2D6 metabolic activity.
Main Results:
- 0.5% aqueous timolol caused greater HR changes than 0.1% hydrogel, especially during exercise.
- Plasma timolol levels correlated with HR changes.
- CYP2D6 poor metabolizers showed higher plasma concentrations and longer elimination half-lives for timolol.
- No significant effects on SAP, DAP, or pulmonary function were observed.
Conclusions:
- Gel formulations of ophthalmic timolol reduce systemic absorption and associated heart rate effects.
- CYP2D6 poor metabolizers may be at higher risk for bradycardia with ophthalmic timolol.
- Systemic effects of ophthalmic timolol are primarily related to heart rate changes.
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