Impact of the beta-1 adrenergic receptor polymorphism on tolerability and efficacy of bisoprolol therapy in Korean heart failure patients: association between beta adrenergic receptor polymorphism and bisoprolol therapy in heart failure (ABBA) study

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.

Spectrofluorimetric determination of bisoprolol fumarate and valsartan in tablets and spiked plasma

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