Effect of chronic exposure to carbon disulfide on biotransformation of phenazone in rabbits.

A significant but reversible inhibition of phenazone elimination was observed in rabbits chronically exposed to CS2. Lack of significant difference of phenazone pharmacokinetics in exposed rabbits 24 h after the last exposure compared with the control group, indicates that alteration of phenazone elimination after chronic exposure to CS2 is reversible. The results obtained with phenazone as a model substance suggest that, during chronic exposure to CS2, elimination of other drugs metabolized by the pathway similar to phenazone may also be altered. This should be taken into account in selecting their dosage.

[Clinical significance of the pharmacogenetics in psychiatric and neurological syndromes]. / Kliniczne znaczenie farmakogenetyki w zespolach psychiatrycznych i neurologicznych.

The aim of the paper was the presentation of the newest results of studies in pharmacogenetics of psychiatric and neurological syndromes. It was especially emphasized an important role of pharmacogenetics in safe pharmacotherapy of psychiatric and neurological syndromes.

[Occurrence of the fast acetylation phenotype in persons with the radicular syndrome. Preliminary report]. / Wystepowanie fenotypu szybkiej acetylacji u osób z zespolem korzeniowym. Doniesienie wstepne.

The polymorphism of drug acetylation is an important factor determining the therapeutic effectiveness and toxicity of the drugs metabolized through acetylation. The purpose of the study was determination of the acetylation phenotype in patients with radicular pain syndromes by means of a test with sulphadimidine acetylation. The test was done in 23 cases of radicular pain syndromes and in 45 healthy volunteers serving as controls. In the control group the fast acetylation phenotype was found in 23 cases (51%) while 22 controls (49%) were slow acetylators. In 23 patients with radicular syndromes 15 (65%) were fast acetylators and 8 (35%) were slow acetylators. The percent of fast and slow acetylators was statistically significantly different between the group of patients and the control group. Mathematical analysis of the results by means of the chi 2 test showed significance of the difference at p less than 0.05. These results may show a predisposition of subjects with fast acetylation phenotype for development of radicular syndromes.

[Clinical significance of the determination of oxidation and acetylation phenotype in patients with multiple sclerosis]. / Kliniczne znaczenie badania fenotypu oksydacji i acetylacji u chorych na stwardnienie rozsiane.

Genetically determined individual differences in the ability of oxidation and acetylation of certain drugs have raised in recent years a considerable interest in view of their clinical importance. The purpose of the study was finding out of a possible difference in the ability to oxidized sparteine and to acetylate sulfamidine as model drugs between patients with multiple sclerosis and healthy control volunteers. The study was carried out in 23 patients with MS. The control group comprised 160 healthy subjects for comparison of oxidation phenotype. The results of determination of acetylation phenotype were obtained in 45 healthy controls. The study showed that in 160 controls 146 were extensive (rapid) metabolizers (91.3%) and 14 were weak (slow) metabolizers of sparteine (8.7%). In the group of MS patients 21 were extensive metabolizers (91.3%) and 2 were weak metabolizers (8.7%). The determination of acetylation phenotype in 45 controls showed 51% of rapid acetylation (23 subjects) and 49% of slow acetylation (22.

[Clinical significance of oxidation and acetylation genetic polymorphism in patients with Parkinson's disease]. / Kliniczne znaczenie polimorfizmu oksydacji sparteiny i acetylacji sulfadimidyny u chorych na chorobe Parkinsona.

The relationship between genetically determined polymorphic oxidation and acetylation and susceptibility to some disease has aroused much interest. The aim of our study was to evaluate whether patients with Parkinson's disease differ from healthy persons in their ability to oxidize sparteine and acetylate sulfadimidine as model drugs. Oxidation and acetylation phenotypes were estimated in 50 patients with Parkinson's disease. The control group consisted of 160 healthy volunteers for comparison of oxidation phenotype and 60 healthy volunteers for comparison of acetylation phenotype. The phenotyping of oxidation revealed two distinct populations among 50 patients with Parkinson's disease: 47 persons (94%) were extensive metabolizers of sparteine and 3 persons (6%) were poor metabolizers. In 160 healthy persons, 146 persons (91.2%) were extensive metabolizers of sparteine and 14 persons (8.8%) were poor metabolizers. The difference between frequency distribution of PMs and EMs in healthy persons and in patients with Parkinson's disease was not statistically significant. The phenotyping of acetylation showed among 50 patients with Parkinson's disease 38 persons (76%) slow acetylators and 12 persons (24%) rapid acetylators. In 60 healthy volunteers the phenotype of slow acetylation was observed in 29 persons (48.3%) and rapid acetylation in 31 persons (51.7%). The prevalence of slow acetylators among patients with Parkinson's disease in comparison to healthy volunteers was statistically significant (chi 2 = 8.7677/p < 0.003). The results of our study may suggest that the slow acetylation phenotype is associated with increased risk of the development of Parkinson's disease.

[Interactions between drugs and results of laboratory tests]. / Interakcje miedzy lekami a wynikami badan laboratoryjnych.

The aim of the paper was the presentation of the newest results of studies on the effects of drugs on clinical laboratory tests. It was especially emphasized an important and clinical significance of these effects of drugs on laboratory tests.

[Biotransformation of phenazone and sulfadimidine as markers of liver metabolism of drug and xenobiotic oxidation and acetylation in women with breast cancer]. / Biotransformacja fenazou i sulfadimidyny jako wskazników watrobowego metabolizmu leków i ksenobiotyków droga utleniania i acetylacji u kobiet chorych na raka sutka.

The aim of our study was to determine phenazone pharmacokinetics as an index of hepatic microsomal enzymes activity and acetylation phenotype in women with breast cancer. Phenazone test was made in 41 women with breast cancer and in 25 healthy women as a control group. Acetylation phenotype was measured in 40 women with breast cancer and in 25 healthy women as a control group. The plasma concentration of phenazone was estimated by the spectrophotometric method of Brodie and associates. Acetylation phenotype was determined by the Bratton-Marshall method in Varley's modification. The mean phenazone half-life time (t0,5), shortened significantly and the mean elimination rate constant (K) increased in women compared with a group of healthy persons. Mean clearance rate was increased in women with breast cancer too, compared with a group of healthy women. Acceleration of phenazone elimination may suggest that in patients with breast cancer elimination of the other drugs metabolized by the pathway similar to phenazone also may be changed. This should be considered in selection of their dosage. We have observed the predominance of rapid acetylators in women with breast cancer comparing with healthy persons. This difference was not statistically significant. Our results of acetylation phenotype in women with breast cancer suggests that rapid acetylation may be a factor of susceptibility to breast cancer.

[Evaluation of phenazone oxidation and sulfadimidine acetylation in patients with hematologic neoplasms]. / Ocena procesów utleniania fenazonu i acetylacji sulfadimidyny u chorych na nowotwory krwi.

The aim of our study was to estimate of phenazone oxidation and sulfadimidine acetylation in patients with Hodgkins disease, non Hodgkins lymphoma and acute leukemia. We observed increase in liver microsomal enzyme activity and predominance of the rapid acetylator phenotype in these pathological states. It should be taken into account when dosing drugs which are metabolized as markers of the liver metabolic efficiency like phenazone and sulphadimidine. One can also expect these patients to have a genetic predisposition to the development of cancer disease.

Acetylator phenotype in patients with allergic diseases and its clinical significance.

The genetic polymorphism of drug acetylation rate in man is an important determinant of the toxic and therapeutic response to certain drugs. This polymorphism can alter not only drug effects but may be a factor influencing the frequency of the occurrence of some disease states. The aim of our study was to establish whether there exists any correlation between the acetylator phenotype and the development of allergic diseases. In patients with allergic diseases and in healthy persons as a control group, the acetylation phenotype was determined by the sulfadimidinic method. In the group of patients with allergic diseases without infectional factor 76% slow and 24% rapid acetylators were found. This predominance of slow acetylators was statistically significant (by using chi 2 test) with comparison to the group of healthy persons, where 49% slow and 51% rapid acetylators were observed. Considerable predominance of slow acetylators in patients with allergic diseases suggest that phenotype of slow acetylation may be a factor playing some role in pathogenesis of allergic diseases and may be a factor predisposing to the development of these diseases.

Genetically determined sparteine oxidation and sulfadimidine acetylation polymorphism in patients with non-occupational urinary bladder cancer.

The results of our study revealed a predominance of the percentage of extensive metabolizers (EM) of sparteine (94.8%) among 58 patients with non-occupational urinary bladder cancer in comparison with the percentage of extensive metabolizers (91.2%) in healthy persons; the difference being not statistically significant. However, among ultrarapid (EM) oxidators with the metabolic ratio (MR) < 0.5 the difference in the MR frequency distribution between 15 patients with bladder cancer (25.9%) and 18 healthy persons (11.25%) was statistically significant. Therefore, our studies provide some evidence of a possible relationship between the EM sparteine oxidation phenotype and the susceptibility to non-occupational bladder cancer. Not statistically significant slight prevalence of the percentage of slow acetylators (SA) (53.1%) among 32 urinary bladder cancer patients in comparison with the percentage of SA (49%) among 45 healthy persons may confirm the conclusion that a slow acetylator phenotype is not associated with the increased risk of the development of non-occupational urinary bladder cancer.

CYP2D6 extensive, intermediate, and poor phenotypes and genotypes in a Polish population.

OBJECTIVE: This study investigated the distribution of the CYP2D6 genotypes and phenotypes in a Polish population and compared the concordance of the two methods. METHODS: Six hundred unrelated healthy individuals from southwestern Poland were studied. The CYP2D6 phenotype was analyzed in 300 individuals using sparteine as a model drug. The CYP2D6 genotype was analyzed in 300 individuals by polymerase chain reaction amplification and restriction fragment length polymorphism techniques for the CYP2D6*1, CYP2D6*3, and CYP2D6*4 alleles. Additionally, in 60 randomly selected healthy individuals both the CYP2D6 phenotype and genotype was assessed to determine accordance between the methods. RESULTS: Of 300 participants in the study 25 (8.3%) were classified as poor metabolizers, 44 (14.7%) as intermediate metabolizers, and 231 (77%) as extensive metabolizers of sparteine. The frequency of CYP2D6*1, CYP2D6*3, and CYP2D6*4 alleles among the genotyped 300 persons was 75.7%, 1.3%, and 23.0%, respectively. The frequency of CYP2D6 deficient genotypes in a Polish population (8.0%) was similar to phenotyping results. The comparison of phenotype and genotype in 60 randomly selected individuals showed a good concordance of the obtained results. CONCLUSIONS. The frequencies of poor metabolizers for CYP2D6 phenotype (8.3%) and genotype (8.0%) in a Polish population from the southwestern region are in concordance and compare well with most results of poor oxidation metabolizers in other white populations.

Genetically determined sparteine oxidation polymorphism in a Polish population.

The genetic oxidation polymorphism was determined in 160 healthy Polish volunteers from the south-west of Poland (Wroclaw region), using sparteine as a model drug. The results of a Polish population study revealed a bimodal distribution of the sparteine metabolic ratio and showed the existence of two oxidation phenotypes designated as extensive and poor metabolizers. The frequency of poor metabolizers in our study (8.8%) compares well with most results of poor oxidation metabolizers in Caucasian populations.