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  • Diclofenac  (1)
  • Electrophysiological study  (1)
  • Springer  (2)
  • 2015-2019
  • 2010-2014
  • 2000-2004  (2)
  • 1960-1964
  • 1920-1924
Collection
Publisher
  • Springer  (2)
Years
  • 2015-2019
  • 2010-2014
  • 2000-2004  (2)
  • 1960-1964
  • 1920-1924
Year
  • 1
    ISSN: 1432-1041
    Keywords: Key words CYP2C9 ; Genetic polymorphism ; Diclofenac
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: Evidence exists to suggest that diclofenac is metabolised by CYP2C9. The present study was undertaken in order to evaluate the effect of the single CYP2C9*3 variant on drug metabolism using diclofenac as a probe drug. Methods: A single dose of diclofenac was administered orally to 12 healthy subjects in whom the genotype of CYP2C9 had been determined previously. The disposition kinetics of diclofenac were compared between homozygotes for the wild type (CYP2C9*1/*1, n=6) and heterozygotes for the Leu359 variant (CYP2C9*1/*3, n=6). Results: For diclofenac, the following kinetic parameters were observed in the CYP2C9*1/*1 and CYP2C9*1/*3 subjects, respectively (mean ± SD): apparent oral clearance (ml/kg/h) 355.8 ± 56.9 and 484.4 ± 155.3; area under plasma concentration–time curve (μg h/ml) 2.7 ± 0.7 and 1.9 ± 0.6. The formation clearance of 4′-hydroxydiclofenac (ml/kg/h) was 63.6 ± 19.1 in the CYP2C9*1/*1 subjects compared with 75.9 ± 27.6 in the CYP2C9*1/*3 subjects. There were no significant differences in any of the kinetic parameters for either diclofenac disposition or formation clearance of 4′-hydroxydiclofenac between the two genotype groups. Conclusion: Since the disposition kinetics of diclofenac does not change in subjects with the single CYP2C9*3 mutant allele, it is suggested that the effects of CYP2C9 polymorphisms on the drug metabolism tend to be substrate specific.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1619-0904
    Keywords: Atrioventricular block ; Intra-Hisian block ; Pacemaker ; Electrophysiological study ; Follow-up
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Long-term follow-up was performed in patients with intra-Hisian atrioventricular (AV) block who were implanted with permanent pacemakers. Subjects were 14 consecutive patients (3 men and 11 women, 65.4±9.7 [SD] years old), who exhibited intra-Hisian block at the time of pacemaker generators were replaced due to battery depletion. Electrophysiological examinations were performed at both the initial implantation and pacemaker replacement. The mean duration from the initial implantation to the replacement was 9.4±4.3 years. All patients had severe symptoms such as syncope, dizziness, or dyspnea, and these symptoms were relieved by pacemaker implantation. Seven patients had complete AV block, and the other seven had advanced or paroxysmal AV block at the time of implantation. Seven patients, who had advanced AV block at the time of implantation, developed complete AV block. Five of the seven patients who had complete AV block at the time of implantation remained in complete AV block, one patient had advanced AV block, and one patient of complete AV block increased significantly from 50% to 93% during the two electrophysiological examinations (P〈0.05). A mean heart rate of 40.3±7.5 beats/min was observed during complete AV block. At the time of implantation, two patients were misdiagnosed as having AH block, and the other two patients were misdiagnosed as having HV block. In conclusion, intra-Hisian AV block gradually developed from advanced or paroxysmal AV block into complete AV block. Because the diagnosis of intra-Hisian block is sometimes difficult, we should always consider the possibility of intra-Hisian block in patients with severely symptomatic AV block.
    Type of Medium: Electronic Resource
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