To evaluate effects of itraconazole, rifampicin and grapefruit juice on pharmacokinetics and pharmacodynamics of a hydrophilic non-selective β-adrenoceptor blocker nadolol, we conducted an open-label, four-way crossover study in 10 healthy male volunteers. A single oral dose of 30 mg nadolol was administered with water (control), itraconazole (100 mg), or grapefruit juice (300 mL), or after a 6-day pretreatment with rifampicin (450 mg/day). Plasma concentrations and urinary excretions of nadolol were measured over 48 hours after its dosing. Systolic and diastolic blood pressures and pulse rate were periodically recorded after nadolol administration as pharmacodynamic parameters. Itraconazole increased the peak plasma concentration and the area under the plasma concentration-time curve (AUC0-∞ ) of nadolol by 468% and 224% of control, respectively (P < .001). A slight, but not statistically significant, decrease in AUC0-∞ of nadolol was observed in rifampicin and grapefruit juice phases as compared to control. Elimination half-life for nadolol did not differ among the four phases. During itraconazole phase, nadolol reduced pharmacodynamic parameters to a greater extent than the other phases. These results suggest that itraconazole substantially increases the oral availability of nadolol possibly by the inhibition of intestinal P-glycoprotein, whereas grapefruit juice has little effect on nadolol pharmacokinetics.
In order to clarify the effects of the Lactococcus lactis (L. lactis) 11/19-B1 strain, a double-blind controlled study of yogurt fermented with the strain was carried out. For the study, two kinds of yogurt, the control and test yogurt, were prepared; the control yogurt was fermented with Streptococcus thermophiles, Lactobacillus delbrueckii subspecies bulgaricus, and Lactobacillus acidophilus, and the test yogurt was enriched with L. lactis 11/19-B1 and Bifidobacterium lactis (B. lactis) BB-12 strains. Seventy-six volunteers who had not received treatment with pharmaceuticals were randomly divided into two groups with each group ingesting 80 g of either the test or control yogurt every day for 8 weeks. Before and after yogurt intake, fasting blood was taken and blood sugar, blood lipids, and anti-cytomegalovirus cellular immunity were estimated. In the test yogurt group, low-density lipoprotein (LDL) was significantly decreased (159.1 ± 25.7 to 149.3 ± 24.4; p = 0.02), but this effect was not observed in the control yogurt group. When the test yogurt group was divided into two groups based on LDL levels of over or under 120 mg/dL, this effect was only observed in the high LDL group. No LDL-lowering effect of B. lactis BB-12 strain was previously reported; therefore, the hypocholesterolemic effects observed in this study are thought to be caused by the L. lactis 11/19-B1 strain alone or its combination with the B. lactis BB-12 strain.
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