The effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of buspirone

OBJECTIVE: The effects of fluvoxamine, a selective serotonin (5-HT) reuptake inhibitor antidepressant, on the pharmacokinetics and pharmacodynamics of buspirone, a non-benzodiazepine anxiolytic agent, were investigated. METHODS: In a randomized, placebo-controlled, two-phase cross-over study, ten healthy volunteers took either 100 mg fluvoxamine or matched placebo orally once daily for 5 days. On day 6, 10 mg buspirone was taken orally. Plasma concentrations of buspirone and its active metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP), were measured up to 18 h and the pharmacodynamic effects of buspirone up to 8 h. RESULTS: The total area under the plasma buspirone concentration-time curve was increased 2.4-fold (P < 0.05) and the peak plasma buspirone concentration 2.0-fold (P < 0.05) by fluvoxamine, compared with placebo. The half-life of buspirone was not affected. The ratio of the total area under the plasma concentration-time curve of 1-PP to that of buspirone was decreased from 7.4 [6.3 (SD)] to 4.4 (3.6) by fluvoxamine (P < 0.05). The results of the six pharmacodynamic tests remained unchanged. CONCLUSION: Fluvoxamine moderately increased plasma buspirone concentrations and decreased the production of the active 1-PP metabolite of buspirone. The mechanism of this interaction is probably inhibition of the CYP3A4-mediated first-pass metabolism of buspirone by fluvoxamine. However, this pharmacokinetic interaction was not associated with impairment of psychomotor performance and it is probably of limited clinical significance.     

Bacterial urovirulence factors and their association with functional and anatomical abnormalities and recurrence of urinary tract infections in children

BACKGROUND: Urinary tract infections in children are associated with functional and anatomical abnormalities of the urinary tract, they tend to recur and can cause permanent kidney damage. AIM: To study in children with urinary tract infections, microbiological factors associated to recurrence, functional and anatomical abnormalities of the urinary tract. PATIENTS AND METHODS: A prospective sample of children was incorporated into a follow-up protocol after their first episode of bacteriologically-demonstrated urinary tract infection. In all patients an abdominal ultrasound examination and a mictional urethrocystography were done and the presence of fimbriae was studied in isolated strains of Escherichia coli. RESULTS: Two hundred fifteen cases bad an adequate adherence to the study protocol, 190 caused by E coli. Fimbriated E coli strains were isolated with greater frequency from children with pyelonephritis than from those with a low urinary tract infection (50 and 28% respectively). The absence of fimbriae in E coli strains was associated with a higher risk of recurrent infections (odds ratio = 3, confidence intervals = 2-9.2) and an abnormal urethrocystography (odds ratio = 3, confidence intervals = 1.1-10.2). CONCLUSIONS: These data are consistent with foreign reports and support the need to study adhesins in E coli strains isolated from children with urinary tract infections.     

Alternative Paths to Competitive Advantage: A Fuzzy-Set Analysis of the Origins of Large Firms

Scholars have documented the importance of national-level factors for the competitive success of firms on a global scale. These studies typically identify multiple factors that are behind the emergence of large and successful firms in particular national clusters. However, there has been relatively little research identifying whether such factors are all collectively necessary to produce the outcome, or whether only a few of the factors in different combinations might be sufficient to generate the shift in competitive advantage manifested in the market power of large “flagship” firms. In this paper, we study the evolution of one industry across six countries in which the competitive position of national firms changed considerably during our 100-year analysis period. The results of our combined historical and fuzzy-set analyses show that an unequal distribution of resources may lead to alternative causal pathways to competitive advantage of the largest firms.