ABSTRACT
BACKGROUND/AIMS: We evaluated the association between coding region variants of adrenergic receptor genes and therapeutic effect in patients with congestive heart failure (CHF). METHODS: One hundred patients with stable CHF (left ventricular ejection fraction [LVEF] < 45%) were enrolled. Enrolled patients started 1.25 mg bisoprolol treatment once daily, then up-titrated to the maximally tolerable dose, at which they were treated for 1 year. RESULTS: Genotypic analysis was carried out, but the results were blinded to the investigators throughout the study period. At position 389 of the beta-1 adrenergic receptor gene (ADRB1), the observed minor Gly allele frequency (Gly389Arg + Gly389Gly) was 0.21, and no deviation from Hardy-Weinberg equilibrium was observed in the genotypic distribution of Arg389Gly (p = 0.75). Heart rate was reduced from 80.8 +/- 14.3 to 70.0 +/- 15.0 beats per minute (p < 0.0001). There was no significant difference in final heart rate across genotypes. However, the Arg389Arg genotype group required significantly more bisoprolol compared to the Gly389X (Gly389Arg + Gly389Gly) group (5.26 +/- 2.62 mg vs. 3.96 +/- 2.05 mg, p = 0.022). There were no significant differences in LVEF changes or remodeling between two groups. Also, changes in exercise capacity and brain natriuretic peptide level were not significant. However, interestingly, there was a two-fold higher rate of readmission (21.2% vs. 10.0%, p = 0.162) and one CHF-related death in the Arg389Arg group. CONCLUSIONS: The ADRB1 Gly389X genotype showed greater response to bisoprolol than the Arg389Arg genotype, suggesting the potential of individually tailoring beta-blocker therapy according to genotype.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Adrenergic beta-1 Receptor Antagonists/adverse effects , Bisoprolol/adverse effects , Gene Frequency , Genotype , Heart Failure/diagnosis , Heart Rate/drug effects , Maximum Tolerated Dose , Pharmacogenomic Testing , Phenotype , Polymorphism, Genetic , Precision Medicine , Receptors, Adrenergic, beta-1/drug effects , Republic of Korea , Stroke Volume/drug effects , Time Factors , Treatment Outcome , Ventricular Function, Left/drug effects , Ventricular Remodeling/drug effectsABSTRACT
Simple, sensitive and rapid spectrofluorimetric procedure is described for the determination of two antihypertensive drugs namely, Bisoprolol fumarate [BSF] and Valsartan [VT]. The effect of solvents was investigated. The fluorescence properties of the two cited drugs showed maximum emission intensity in 0.1N H[2]SO[4] at lambda [em] 298 and 415nm for BSF and VT, respectively, when excited at lambda[ex] 227nm. The calibration graphs were rectilinear from 0.08-1.28 and 0.12-1.6 micro g/ml for BSF and VT respectively. The method, was applied to the determination of the two cited drugs in tablets either single or when co-formulated with hydrochlorothiazide [HZ] with % recoveries of 100.03 +/- 0.57 and 99.70 +/- 0.90 for BSF and VT, respectively. Furthermore, the high sensitivity of the proposed method it allowed its application in spiked human plasma with good % recoveries of 99.73 +/- 2.06 for BSF and 99.94 +/- 1.71 for VT