Effect of CYP2D6*4, CYP2D6*10 polymorphisms on the safety of treatment with timolol maleate in patients with glaucoma.

Abstract

Timolol maleate is used for the treatment of glaucoma and metabolized by cytochrome CYP2D6 in the liver. The aim of this study was the evaluation of the influence of CYP2D6*4 and CYP2D6*10 gene polymorphisms on the safety of medications containing 0.5% of timolol maleate as glaucoma treatment in patients with primary open-angle glaucoma (POAG). 105 patients with POAG were prescribed glaucoma medications, containing 0.5% timolol maleate. The safety of glaucoma treatment was determined by electrocardiography (ECG) (to assess heart rate (HR) and PQ interval) and blood pressure (BP) measurements. The real-time polymerase chain reaction method was used for the detection of single nucleotide polymorphisms (SNP). The risk of adverse drug reactions was higher in patients with the CYP2D6*4GA genotype compared with GG: mean HR change at 1month (2.88±4.68 and 6.44±5.57, p<0.001) and 6months (5.14±8.93 and 7.88±5.65, p<0.001), mean PQ interval change at 1 (0.01±0.031 and 0.02±0.022, p=0.003) and 6months (0.01±0.032 and 0.02±0.024, p=0.003). The risk of adverse drug reactions was higher in patients with the CYP2D6*10 CT genotype compared with CC: mean HR change at 1month (2.94±4.65 and 6.34±5.66, p<0.001) and 6months (5.20±8.90 and 7.78±5.75, p<0.001), mean PQ interval change at 1 (0.01±0.032 and 0.02±0.021, p=0.014) and 6months (0.01±0.033 and 0.02±0.022, p=0.014). CYP2D6*4 and CYP2D6*10 gene polymorphisms may affect a higher risk of timolol-induced bradycardia and increased PQ interval of treatment medications containing 0.5% of timolol maleate in patients with POAG.