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Digitale Medien

Frequency of cytochrome P 450 3A4 variant genotype in transplant population and lack of association with cyclosporin clearance (2000)

Rivory, L. P. ; Qin, H. ; Clarke, S. J. ; [weitere]

Springer

European journal of clinical pharmacology 56 (2000), S. 395-398

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ISSN: 1432-1041

Schlagwort(e): Key words Cytochrome P450 3A4 ; Cyclosporin ; Transplant

Quelle: Springer Online Journal Archives 1860-2000

Thema: Chemie und Pharmazie , Medizin

Notizen: Abstract Objective: Cytochrome P 450 3A4 (CYP3A4) plays a vital role in the oxidative metabolism of many xenobiotics. Some recent reports have provided circumstantial evidence in support of an association between a genetic polymorphism (A→G) in the 5′-flanking region (−290) of CYP3A4 and altered enzyme activity. We sought to determine whether genotyping patients for CYP3A4-G could assist with the dose optimisation of drugs metabolised by this system. Methods: Normal subjects and renal-transplant patients receiving cyclosporin for immune modulation were genotyped for the CYP3A4-G variant. A surrogate for cyclosporin clearance was estimated from the ratio of the cyclosporin dose, normalised for body weight and the corresponding trough concentration. The association between genotype and clearance was examined in patients who received twice-daily doses of cyclosporin and who were not on concurrent medication known to modify CYP3A4 function. Results: The allelic frequencies of the CYP3A4-G variant were estimated to be 2.6% and 3% in transplant patients and normal subjects, respectively. The median cyclosporin pseudo-clearance of transplant patients with wild-type CYP3A4 was 0.90 l/h/kg (range: 0.35–3.8 l/h/kg; n=86), whereas the corresponding value for the five patients heterozygotic for the CYP3A4-G variant was 0.71 l/h/kg (range 0.35–0.91 l/h/kg). The distribution of the pseudo-clearance according to genotype was not found to be significant according to a Fisher's exact test (P=0.15). Conclusion: Genotyping for the CYP3A4-G polymorphism is unlikely to assist cyclosporin dose selection in transplant patients.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1007/s002280000166

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Digitale Medien

Preparation of monodispersed plate-like particles of tungstic acid (1998)

Brown, A. B. D. ; Clarke, S. M. ; Rennie, A. R.

Springer

Colloid & polymer science 276 (1998), S. 549-552

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ISSN: 1435-1536

Schlagwort(e): Key words Disc-shaped particles ; colloidal dispersion ; flocs ; tungsten oxide

Quelle: Springer Online Journal Archives 1860-2000

Thema: Chemie und Pharmazie , Maschinenbau

Notizen: Abstract To understand the properties of colloidal dispersions it is often vital to prepare model materials with particles that have a small polydispersity in order to make experimental tests of theories or models. However few preparations have been developed that yield anisotropic particles with a narrow size distribution and precise shape. In this paper the preparation of a dispersion of charge stabilized, tungstic acid particles is described. The particles are rectangular and have a length of 7.0 μm, a width of 2.8 μm and a thickness of 0.2 μm. The polydispersity is 8% in length and 10% in width, making it one of the most monodisperse dispersions of anisotropic particles. Each particle is monocrystalline and the crystal orientation is fixed with respect to the particle morphology. Some interesting behavior is observed: these particles aggregate perpendicular and parallel to each other to give flat, ordered flocs when the stability is reduced.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1007/s003960050280

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